60 results on '"Guo-Lin Chen"'
Search Results
2. Extensive alternative splicing of the repressor element silencing transcription factor linked to cancer.
- Author
-
Guo-Lin Chen and Gregory M Miller
- Subjects
Medicine ,Science - Abstract
The repressor element silencing transcription factor (REST) is a coordinate transcriptional and epigenetic regulator which functions as a tumor suppressor or an oncogene depending on cellular context, and a truncated splice variant REST4 has been linked to various types of cancer. We performed a comprehensive analysis of alternative splicing (AS) of REST by rapid amplification of cDNA ends and PCR amplification of cDNAs from various tissues and cell lines with specific primers. We identified 8 novel alternative exons including an alternate last exon which doubles the REST gene boundary, along with numerous 5'/3' splice sites and ends in the constitutive exons. With the combination of various splicing patterns (e.g. exon skipping and alternative usage of the first and last exons) that are predictive of altered REST activity, at least 45 alternatively spliced variants of coding and non-coding mRNA were expressed in a species- and cell-type/tissue-specific manner with individual differences. By examining the repertoire of REST pre-mRNA splicing in 27 patients with kidney, liver and lung cancer, we found that all patients without exception showed differential expression of various REST splice variants between paired tumor and adjacent normal tissues, with striking cell-type/tissue and individual differences. Moreover, we revealed that exon 3 skipping, which causes no frame shift but loss of a domain essential for nuclear translocation, was affected by pioglitazone, a highly selective activator of the peroxisome proliferator-activated receptor gamma (PPARγ) which contributes to cell differentiation and tumorigenesis besides its metabolic actions. Accordingly, this study demonstrates an extensive AS of REST pre-mRNA which redefines REST gene boundary and structure, along with a general but differential link between REST pre-mRNA splicing and various types of cancer. These findings advance our understanding of the complex, context-dependent regulation of REST gene expression and function, and provide potential biomarkers and therapeutic targets for cancer.
- Published
- 2013
- Full Text
- View/download PDF
3. Perturbations of Neuron-Restrictive Silencing Factor Modulate Corticotropin-Releasing Hormone Gene Expression in the Human Cell Line BeWo
- Author
-
Vasileios Kreouzis, Guo-Lin Chen, and Gregory M. Miller
- Subjects
Original Paper ,endocrine system ,Regulator ,Neuropeptide ,General Medicine ,Biology ,Cell biology ,Corticotropin-releasing hormone ,Hypothalamus ,Gene expression ,Gene silencing ,Epigenetics ,Regulatory Pathway ,hormones, hormone substitutes, and hormone antagonists - Abstract
Stress exacerbates disease, and understanding its molecular mechanisms is crucial to the development of novel therapeutic interventions to combat stress-related disorders. The driver of the stress response in the hypothalamic-pituitary-adrenal axis (HPA) is corticotropin-releasing hormone (CRH), a neuropeptide synthesized in the paraventricular nucleus of the hypothalamus. Evidence supports that CRH expression is epigenetically modified at the molecular level by environmental stimuli, causing changes in the stress response. This effect is mediated by a concert of factors that translate environmental change into alterations in gene expression. An important regulator and epigenetic modulator of CRH expression is neuron-restrictive silencing factor (NRSF). Previously, our lab identified numerous splice variants of NRSF that are specific to humans and predictive of differential regulatory effects of NRSF variants on targeted gene expression. The human cell line BeWo has endogenous CRH and NRSF expression providing an in vitro model system. Here, we show that manipulation of NRSF expression through siRNA technology, overexpression by plasmid vectors, and direct cAMP induction that CRH expression is linked to changes in NRSF expression. Accordingly, this epigenetic regulatory pathway in humans might be a critical mechanism involved in the regulation of the stress response.
- Published
- 2018
4. Determination of gastrodin level in serum containing formula for calming the liver and suppressing yang and investigation of drug serum effects on vascular smooth muscle cell avtivity in rats
- Author
-
Xiang-ping, Li, Yan-hong, Luo, Guang-wei, Zhong, Tao, Yin, Ling-li, Xiang, Wei, Li, and Guo-lin, Chen
- Published
- 2010
- Full Text
- View/download PDF
5. Modulation of nuclear REST by alternative splicing: a potential therapeutic target for Huntington's disease
- Author
-
Jianyu Shang, Guo-Lin Chen, Gregory M. Miller, Dharmendra Goswami, and Qi Ma
- Subjects
0301 basic medicine ,Huntingtin ,PPARγ ,Morpholino ,nuclear translocation ,Repressor ,Biology ,Models, Biological ,REST/NRSF ,Cell Line ,Morpholinos ,alternative splicing ,Stmn2 ,Mice ,03 medical and health sciences ,Gene expression ,Transcriptional regulation ,Animals ,Humans ,Gene silencing ,Molecular Targeted Therapy ,RNA, Small Interfering ,Syn‐1 ,Transcription factor ,Cell Nucleus ,Neurons ,antisense oligos ,Calcium-Binding Proteins ,Alternative splicing ,Intracellular Signaling Peptides and Proteins ,Huntington's disease ,Original Articles ,Exons ,Cell Biology ,gene therapy ,Molecular biology ,Corpus Striatum ,3. Good health ,Cell biology ,PPAR gamma ,Repressor Proteins ,Huntington Disease ,030104 developmental biology ,Stathmin ,Molecular Medicine ,Original Article ,Signal Transduction - Abstract
Huntington's disease (HD) is caused by a genetically mutated huntingtin (mHtt) protein with expanded polyQ stretch, which impairs cytosolic sequestration of the repressor element‐1 silencing transcription factor (REST), resulting in excessive nuclear REST and subsequent repression of neuronal genes. We recently demonstrated that REST undergoes extensive, context‐dependent alternative splicing, of which exon‐3 skipping (∆E3)—a common event in human and nonhuman primates—causes loss of a motif critical for REST nuclear targeting. This study aimed to determine whether ∆E3 can be targeted to reduce nuclear REST and rescue neuronal gene expression in mouse striatal‐derived, mHtt‐expressing STHdhQ111/Q111 cells—a well‐established cellular model of HD. We designed two morpholino antisense oligos (ASOs) targeting the splice sites of Rest E3 and examined their effects on ∆E3, nuclear Rest accumulation and Rest‐controlled gene expression in STHdhQ111/Q111 cells. We found that (1) the ASOs treatment significantly induced ∆E3, reduced nuclear Rest, and rescued transcription and/or mis‐splicing of specific neuronal genes (e.g. Syn1 and Stmn2) in STHdhQ111/Q111 cells; and (2) the ASOs‐induced transcriptional regulation was dependent on ∆E3 induction and mimicked by siRNA‐mediated knock‐down of Rest expression. Our findings demonstrate modulation of nuclear REST by ∆E3 and its potential as a new therapeutic target for HD and provide new insights into environmental regulation of genome function and pathogenesis of HD. As ∆E3 is modulated by cellular signalling and linked to various types of cancer, we anticipate that ∆E3 contributes to environmentally tuned REST function and may have a broad range of clinical implications.
- Published
- 2017
6. Alternative REST Splicing Underappreciated
- Author
-
Guo-Lin Chen and Gregory M. Miller
- Subjects
Gene isoform ,Genetics ,0303 health sciences ,General Neuroscience ,Alternative splicing ,General Medicine ,Epigenome ,Biology ,Cell biology ,03 medical and health sciences ,Exon ,0302 clinical medicine ,Gene expression ,RNA splicing ,Gene silencing ,Epigenetics ,Gene ,Transcription factor ,030217 neurology & neurosurgery ,030304 developmental biology - Abstract
As a major orchestrator of the cellular epigenome, the repressor element-1 silencing transcription factor (REST) can either repress or activate thousands of genes depending on cellular context, suggesting a highly context-dependent REST function tuned by environmental cues. While REST shows cell-type non-selective active transcription (Kojima et al., 2001), an N-terminal REST4 isoform caused by alternative splicing, inclusion of an extra exon (N3c) which introduces a pre-mature stop codon, contributes to neurogenesis and tumorigenesis (Palm et al., 1998, 1999; Lee et al., 2000; Raj et al., 2011). Recently, in line with established epigenetic regulation of pre-mRNA splicing (Allo et al., 2010; Luco et al., 2011), we demonstrated that REST undergoes extensive, context-dependent alternative splicing which results in the formation of a large number of mRNA variants predictive of multiple protein isoforms (Chen and Miller, 2013). Supported by the fact that immunoblotting/-staining with different anti-REST antibodies yield different results, alternative splicing allows production of various structurally and functionally different REST protein isoforms in response to shifting physiologic requirements, shedding light on environmental regulation of REST function. However, REST isoforms might be differentially assayed or manipulated, leading to data misinterpretation and controversial findings. For example, in contrast to the proposed neurotoxicity of elevated nuclear REST in ischemia (Noh et al., 2012) and Huntington’s disease (Zuccato et al., 2003; Buckley et al., 2010), Lu et al. recently reported decreased nuclear REST in Alzheimer’s disease and neuroprotection of REST in aging brain (Lu et al., 2014). Unfortunately, alternative REST splicing was largely neglected by Lu et al. (2014), making it necessary for a reevaluation of their findings. As shown in Figure 1 A , human REST gene boundary is now doubled by an alternative …
- Published
- 2017
7. Transient Response Enhancement with Fast Transient Controller for Capacitor-Less LDO Regulator
- Author
-
Shang Sheng Chi, Guo Lin Chen, Wei Hu, Ming Hui Fan, and Yu Sen Xu
- Subjects
Low-dropout regulator ,Materials science ,Dropout voltage ,Control theory ,Settling time ,Overshoot (signal) ,General Medicine ,Transient response ,Transient (oscillation) ,Voltage - Abstract
This paper presents a capacitor-less CMOS low dropout regulator (LDO) with a push-pull class AB amplifier, and a fast transient controller to achieve a better transient response. The undershoot/overshoot voltage and the settling time are effectively reduced. Through the theoretical analysis of the circuit, cadence simulation with SMIC 0.18μm process and under the condition of the input voltage range 1.4~4 V shows the output voltage is 1.2 V, with the fast controller the total quiescent current is 8.2 μA, the undershoot /overshoot voltage is 97 mV/47 mV and the settling time is 0.3 μs as load current suddenly changes from 1 to 100 mA, or vice versa. Compared with this paper without fast transient controller, the undershoot voltage, the overshoot voltage and the settling time are enhanced by 30%, 64% and 80%, respectively.
- Published
- 2014
8. The Feasibility of Producing Green Energy Crops on Pb-Contaminated Soil
- Author
-
Sheng Jie Lin, Jia Rong Chen, Guo Lin Chen, Chi Ying Lai, Yao Ting Tu, Shu Fen Cheng, and Chin Yuan Huang
- Subjects
Energy crop ,Phytoremediation ,Agronomy ,Agricultural land ,business.industry ,Environmental remediation ,General Engineering ,Biomass ,Environmental science ,Sowing ,business ,Soil contamination ,Renewable energy - Abstract
For the agricultural land contaminated by heavy metal and thus not suitable for growing food crops, combining green crops with phytoremediation technology can provide more green energy crops and implement the soil remediation through a more economic green remediation method. This study selected three crops, which are rich in biomass energy and are suitable to grow in the climatic conditions of Taiwan, namely corn, soybean and peanut, for Pb-contaminated soil situ vegetation planting tests. The results show that the production of biomass by corn was the highest and each plant could produce 1248 g on average, followed by peanut with the average 470.2 g, soybean only 17.6 g. Regarding Pb absorption capacity, each corn could absorb 87.1 mg; peanut 125.3 mg; and soybean only 5.9 mg. Soybean is not feasible because the low biomass production and the total Pb absorption are far lower than those of corn and peanut.
- Published
- 2013
9. Rhesus monkey tryptophan hydroxylase-2 coding region haplotypes affect mRNA stability
- Author
-
Gregory M. Miller and Guo-Lin Chen
- Subjects
Nonsynonymous substitution ,RNA Stability ,Molecular Sequence Data ,Single-nucleotide polymorphism ,Tryptophan Hydroxylase ,Biology ,PC12 Cells ,Polymorphism, Single Nucleotide ,Article ,Gene expression ,Animals ,Coding region ,Amino Acid Sequence ,RNA, Messenger ,Neurons ,Genetics ,Messenger RNA ,TPH2 ,Phosphatidylethanolamines ,General Neuroscience ,Haplotype ,Tryptophan hydroxylase ,Macaca mulatta ,Molecular biology ,Rats ,Haplotypes ,Nucleic Acid Conformation - Abstract
Tryptophan hydroxylase-2 (TPH2) synthesizes neuronal 5-HT and its genetic variance is associated with numerous behavioral traits and psychiatric disorders. This study characterized the functional significance of two nonsynonymous single nucleotide polymorphisms (SNPs) (C74A and G223A) in rhesus monkey TPH2 (mTPH2). Four haplotypes of mTPH2 were cloned into pcDNA3.1 and stably transfected into PC12 cells. The levels of mTPH2 mRNA and protein were assessed by quantitative real-time PCR and Western blot, respectively, while the intracellular 5-HT was measured by enzyme-linked immunosorbent assay (ELISA). The variant A-A haplotype showed significantly higher levels of mTPH2 mRNA and protein, as well as significantly higher 5-HT production than the wild-type C-G haplotype, while the other two variant haplotypes (C-A and A-G) also tended to produce more 5-HT than C-G haplotype when stably expressed in PC12 cells. Both C74A and G223A were predicted to change mRNA secondary structure, and analysis of the mRNA stability showed that the wild-type C-G haplotype mRNA degrades more quickly than mRNAs of the mutant mTPH2 haplotypes in both stable PC12 and transient HEK-293 cells. This study demonstrates that nonsynonymous SNPs in mTPH2 can affect mRNA stability. Our findings provide an additional mechanism by which nonsynonymous SNPs affect TPH2 function, and further our understanding of TPH2 gene expression regulation.
- Published
- 2008
10. Functional characterization of the human TPH2 5′ regulatory region: untranslated region and polymorphisms modulate gene expression in vitro
- Author
-
Guo-Lin Chen, Eric J. Vallender, and Gregory M. Miller
- Subjects
Untranslated region ,Gene isoform ,5' Flanking Region ,Molecular Sequence Data ,5' flanking region ,Tryptophan Hydroxylase ,Biology ,Polymorphism, Single Nucleotide ,Article ,Sequence Homology, Nucleic Acid ,Gene expression ,Genetics ,Animals ,Humans ,Electrophoretic mobility shift assay ,Promoter Regions, Genetic ,Cells, Cultured ,Genetics (clinical) ,Regulation of gene expression ,Base Sequence ,Haplotype ,RNA-Binding Proteins ,Promoter ,Embryo, Mammalian ,Molecular biology ,Rats ,DNA-Binding Proteins ,Gene Expression Regulation ,Nucleic Acid Conformation ,5' Untranslated Regions - Abstract
Tryptophan hydroxylase-2 (TPH2) is a recently identified TPH isoform responsible for neuronal serotonin (5-HT) synthesis, and TPH2 polymorphisms are associated with a range of behavioral traits and psychiatric disorders. This study characterized cis-acting elements and three common polymorphisms (-703G/T, -473T/A, and 90A/G) in the 5' regulatory region of human TPH2 by using luciferase reporter assay, quantitative real-time PCR, and electrophoretic mobility shift assay (EMSA). The core promoter of human TPH2 was localized to the region between -107 and +7, and the segment of +8 to +53 within the 5'-UTR was found to exert a potent inhibitory effect on gene expression at both transcriptional and post-transcriptional levels. In both RN46A and HEK-293 cell lines, the TTA (-703T/-473T/90A) haplotype of the three polymorphisms showed the lowest gene expression compared with other haplotypes, and the -703G/T and -473T/A polymorphisms tended to exert a synergic effect on gene expression dependent upon the sequence of the 5'-UTR. In RN46A, the 90A/G polymorphism significantly increased luciferase activity and mRNA level irrespective of the other two polymorphisms, while in HEK-293 cells the effect of 90A/G was dependent on the alleles at loci -703 and -473. EMSA showed that all the three polymorphisms potentially alter DNA-protein interactions, while the 90A/G polymorphism predictably alters the 5'-UTR secondary structure of mRNA and influences RNA-protein interactions. In conclusion, our present study demonstrates that both the 5'-UTR and common polymorphisms (especially the 90A/G) in the 5' regulatory region of human TPH2 have a significant impact on gene expression.
- Published
- 2007
11. Rhesus Monkey Trace Amine-Associated Receptor 1 Signaling: Enhancement by Monoamine Transporters and Attenuation by the D2 Autoreceptor in Vitro
- Author
-
Hong Yang, Wei-Dong Yao, Mary E. Bahn, Gregory M. Miller, Susan V. Westmoreland, Bertha K. Madras, Eric J. Vallender, Guo-Lin Chen, and Zhihua Xie
- Subjects
Blotting, Western ,Fluorescent Antibody Technique ,Biology ,Pharmacology ,Transfection ,Receptors, G-Protein-Coupled ,Radioligand Assay ,Dopamine receptor D1 ,Genes, Reporter ,Dopamine receptor D3 ,Dopamine receptor D2 ,TAAR1 ,Monoaminergic ,Animals ,RNA, Messenger ,Luciferases ,Cells, Cultured ,Autoreceptors ,Dopamine transporter ,Neurons ,Dopamine Plasma Membrane Transport Proteins ,Receptors, Dopamine D2 ,Reverse Transcriptase Polymerase Chain Reaction ,Receptors, Dopamine D1 ,Dopaminergic ,Immunohistochemistry ,Macaca mulatta ,Substantia Nigra ,Amphetamine ,Monoamine neurotransmitter ,biology.protein ,Molecular Medicine ,Central Nervous System Stimulants ,Electrophoresis, Polyacrylamide Gel ,Proto-Oncogene Proteins c-fos ,Signal Transduction - Abstract
Trace amine-associated receptor 1 (TAAR1) is a G protein-coupled receptor that directly responds to endogenous monoamines as well as amphetamine-related psychostimulants, including methamphetamine. In the present study, we demonstrate TAAR1 mRNA and protein expression in rhesus monkey brain regions associated with monoaminergic systems, variable cellular distribution of TAAR1 in rhesus monkey brain, and TAAR1 coexpression with the dopamine transporter (DAT) in a subset of dopamine neurons in both rhesus monkey and mouse substantia nigra. On this basis, we evaluated rhesus monkey TAAR1 activation by different compounds and its functional relation with monoamine transporters and the dopamine D2 receptor (D2) short isoform (D2s) autoreceptor in vitro using a cAMP response element-luciferase assay. TAAR1 activation by monoamines and amphetamine-related compounds was greatly enhanced by coexpression of dopamine, norepinephrine, or serotonin transporters, and the activation enhancement was blocked by monoamine transporter inhibitors. This enhancement did not occur in control experiments in which the dopamine D1 receptor (D1) was substituted for TAAR1. Furthermore, activation of TAAR1 by dopamine was completely inhibited by D2s when coexpressed with TAAR1, and this inhibition was blocked by the D2 antagonist raclopride. Last, dopamine activation of TAAR1 could induce c-FOS-luciferase expression but only in the presence of DAT, whereas dopamine activation of D1 resulted in equivalent c-FOS expression in the presence or absence of DAT. Together, these data reveal a broad agonist spectrum for TAAR1, a functional relation of TAAR1 with monoamine transporters and D2s, and a mechanism by which D2 receptor drugs can influence brain monoaminergic function and have efficacy through affecting TAAR1 signaling.
- Published
- 2007
12. Tryptophan hydroxylase-2 gene polymorphisms in rhesus monkeys: association with hypothalamic–pituitary–adrenal axis function and in vitro gene expression
- Author
-
Gregory M. Miller, Melinda A. Novak, Guo-Lin Chen, Xie Z, and S. Hakim
- Subjects
Male ,Hypothalamo-Hypophyseal System ,Hydrocortisone ,Molecular Sequence Data ,Pituitary-Adrenal System ,Single-nucleotide polymorphism ,Tryptophan Hydroxylase ,Biology ,Linkage Disequilibrium ,Cellular and Molecular Neuroscience ,Exon ,Sequence Homology, Nucleic Acid ,Genotype ,Gene expression ,Animals ,Amino Acid Sequence ,3' Untranslated Regions ,Molecular Biology ,Gene ,Cells, Cultured ,Polymorphism, Genetic ,Base Sequence ,TPH2 ,Gene Expression Profiling ,Haplotype ,DNA ,Tryptophan hydroxylase ,Macaca mulatta ,Molecular biology ,Circadian Rhythm ,Psychiatry and Mental health ,Phenotype ,Gene Expression Regulation - Abstract
Tryptophan hydroxylase-2 (TPH2) is a newly identified second form of TPH responsible for serotonin synthesis in the brain and has been increasingly implicated as a contributor to the etiology of various psychiatric disorders. In this study, we have identified the constellation of polymorphisms in rhesus monkey TPH2 and investigated genotype/phenotype association as well as gene expression effects of specific polymorphisms. Genomic DNA was obtained from 247 rhesus monkeys, among which 24 had been previously examined for plasma cortisol level, dexamethasone suppression, and combined dexmethasone/ACTH challenge. Polymorphisms in all exons, splicing junctions and approximately 2 kb of the 5′-flanking region (5′-FR) of TPH2 were identified by sequencing. We identified 17 single nucleotide polymorphisms (SNPs) including two that are predictive of amino-acid change (25Pro>His and 75Gly>Ser, respectively), two mononucleotide repeats, one dinucleotide repeat, and one 159-bp insertion polymorphism. The 3′-UTR polymorphisms were significantly associated with hypothalamic–pituitary–adrenal (HPA) axis activity, especially 2051A>C, which was strikingly correlated with plasma cortisol level in the morning only (F=10.203, P=0.001). Luciferase reporter gene assays showed that the 3′-UTR polymorphisms and haplotypes had a profound effect on in vitro gene expression. Accordingly, these investigations revealed that polymorphisms in 3′-UTR of rhesus monkey TPH2 modulate HPA axis function, presumably by affecting levels of TPH2 expression.
- Published
- 2006
13. Endogenous Histamine and Cortisol Levels in Subjects with Different Histamine N-Methyltransferase C314T Genotypes
- Author
-
Vicky Spratlin, Hong-Hao Zhou, Yuen Yi Hon, Gan Zhou, Guo-Lin Chen, Dong Guo, Michael W. Jann, and William J. Jusko
- Subjects
Adult ,Male ,Histamine N-Methyltransferase ,medicine.medical_specialty ,Genotype ,Hydrocortisone ,Pilot Projects ,Endogeny ,Biology ,Article ,chemistry.chemical_compound ,Internal medicine ,Genetics ,medicine ,Humans ,Allele ,Whole blood ,Pharmacology ,Polymorphism, Genetic ,Histamine N-methyltransferase ,Heterozygote advantage ,General Medicine ,Endocrinology ,chemistry ,Molecular Medicine ,Female ,Histamine ,medicine.drug - Abstract
Background: Histamine N-methyltransferase (HNMT) catalyzes the methylation of histamine and plays an important role in histamine biotransformation in bronchial epithelium. Enzymatic activity of HNMT has been shown to be regulated by genetic factors, including polymorphisms in the HNMT gene. In this pilot study we determined endogenous levels of histamine and cortisol in plasma and whole blood samples from subjects with different genotypes for the HNMT C314T polymorphism, and investigated whether these parameters differed between individuals with the HNMT CC genotype and those with the CT genotype. Methods: Blood samples were collected from 48 unrelated volunteers (36 males, 12 females), aged 21–40 years, who participated in the study. PCR-restriction fragment length polymorphism analysis was used to determine HNMT C314T genotypes. Erythrocyte HNMT activity was determined as well as plasma and whole blood levels of histamine and cortisol. Two-group comparisons of the various parameters were analyzed by Blocked Wilcoxon test and Wilcoxon Rank Sum test as appropriate. Results: Thirty-seven subjects (24 Caucasians, three African Americans, one Middle Eastern, five Indians, three Chinese, and one Filipino) were found to have the homozygous CC genotype. Ten subjects (eight Caucasians, one Middle Eastern, and one Chinese) were heterozygous and one individual (Pakistani) was homozygous for the variant 314T allele. The frequency of HNMT CI heterozygotes in the small Caucasian cohort was 0.125. Median enzyme activity was significantly lower in subjects with the heterozygous CT genotype than in those with the homozygous CC genotype (485 vs 631 U/mL of red blood cells; p = 0.023). A broad range of histamine levels in plasma and whole blood was observed for all subjects. Whereas the median plasma histamine level was found to be higher in heterozygotes for the wild-type 314C allele than homozygotes (3.32 vs 2.30 nmol/L; p = 0.021), there was no difference between the two groups in histamine levels in whole blood. Cortisol levels were similar between individuals with the homozygous CC genotype and those with the heterozygous CT genotype. Conclusion: Wide variability of plasma and whole-blood histamine levels was observed in subjects with different HNMT C314T genotypes. Endogenous levels of histamine are likely to be affected by various genes and polymorphisms.
- Published
- 2006
14. MDR1 genotype do not influence the absorption of a single oral dose of 100 mg talinolol in healthy Chinese males
- Author
-
Guo-Lin Chen, Dong-Li Hu, Zhi-Rong Tan, Hong-Hao Zhou, Wei-Xia Zhang, Gan Zhou, Jie Liu, and Wei-Zhang
- Subjects
Male ,Linkage disequilibrium ,Genotype ,Adrenergic beta-Antagonists ,Clinical Biochemistry ,Administration, Oral ,Single-nucleotide polymorphism ,Pharmacology ,Polymerase Chain Reaction ,Polymorphism, Single Nucleotide ,Biochemistry ,Propanolamines ,chemistry.chemical_compound ,Exon ,Pharmacokinetics ,Reference Values ,Polymorphism (computer science) ,Humans ,Medicine ,ATP Binding Cassette Transporter, Subfamily B, Member 1 ,business.industry ,Biochemistry (medical) ,Exons ,General Medicine ,Venous blood ,chemistry ,Area Under Curve ,business ,Polymorphism, Restriction Fragment Length ,Talinolol - Abstract
Objective We investigated the linkage between SNPs in exon 12 (C1236T), exon 21 (G2677T/A) and exon 26 (C3435T) of MDR1, and explored the effect of linked polymorphism on the absorption of talinolol after a single oral dose of 100 mg. Methods The genotype of 192 healthy Chinese volunteers was determined using PCR-RFLP with respect to the MDR1 alleles of interest, C1236T, G2677T/A and C3435T. Linkage disequilibrium was analyzed using PHASE software. Consecutive eligible subjects received a single oral dose of 100 mg talinolol. Venous blood samples were taken at intervals up to 60 h post dose for HPLC analysis of plasma concentration of talinolol to obtain a pharmacokinetic profile. Results Linkage disequilibrium existed between exon 21 (G2677T/A) and exon 26 (C3435T), exon 12 (C1236T) and exon 21 (G2677T/A), but not between exon 12 (C1236T) and exon 21 (G2677T/A). AUC (0,3h), AUC (0,∞), C max and C max /AUC (0,∞), used as indices of talinolol absorption, were not significantly different between the genotype groups of 2677GG/3435TT, 2677TT/3435TT, 2677GT/3435CT and 2677AT/3435CT. For these 4 groups, AUC(0,3h) were 436.8 ± 50.1, 510.1 ± 86.3, 466.1 ± 77.8 and 437.2 ± 73.4 (μg × h/l) and the C max /AUC (0,∞) were 0.097 ± 0.018, 0.093 ± 0.022, 0.105 ± 0.014 and 0.102 ± 0.027 (h −1 ), respectively. ( P > 0.05). Conclusions The linked MDR1 polymorphisms in exon 21 G2677T/A and exon 26 C3435T apparently did not contribute to the absorptive pharmacokinetics of a single oral dose of 100 mg talinolol.
- Published
- 2005
15. The Influence of St. John's Wort on CYP2C19 Activity with Respect to Genotype
- Author
-
Dan Wang, Guo-Lin Chen, Gan Zhou, Wang An, Hong-Hao Zhou, A. M. Abd El-Aty, Lian-Sheng Wang, Jie Liu, Qing Li, Bing Zhu, Zhi Li, Jun Wu, and Zhi Rong Tang
- Subjects
Adult ,Male ,Genotype ,CYP2C19 ,Pharmacology ,Placebo ,Mixed Function Oxygenases ,Excretion ,chemistry.chemical_compound ,Cytochrome P-450 CYP1A2 ,Caffeine ,medicine ,Humans ,Pharmacology (medical) ,Mephenytoin ,Cross-Over Studies ,Polymorphism, Genetic ,biology ,Plant Extracts ,business.industry ,CYP1A2 ,Cytochrome P450 ,Crossover study ,humanities ,Cytochrome P-450 CYP2C19 ,chemistry ,biology.protein ,Aryl Hydrocarbon Hydroxylases ,business ,Hypericum ,medicine.drug - Abstract
Induction of cytochrome p450 isozymes is the major cause for clinical drug interactions of St. John's wort. The relationships of St. John's wort to cytochrome p450 isoforms have been fully investigated, but its effect on CYP2C19 is lacking. Thus, the aim of the present study was to observe the effect of St. John's wort on CYP2C19 activity using CYP1A2 as a control. Twelve healthy adult men-6 extensive metabolizers of CYP2C19 (2C19(*)1/2C19(*)1) and 6 poor metabolizers (4 2C19(*)2/2C19(*)2 and 2 2C19(*)2/2C19(*)3)-were enrolled in a two-phase, randomized, crossover manner. All subjects took a 300-mg St. John's wort tablet or placebo three times daily for 14 days, and then the activities of CYP2C19 and CYP1A2 were measured using mephenytoin and caffeine. It was found that St. John's wort treatment significantly increased CYP2C19 activity in CYP2C19 wild-genotype subjects, with urinary 4'-hydroxymephenytoin excretion raised by 151.5% +/- 91.9% (p = 0.0156), whereas no significant alteration was observed for CYP2C19 poor metabolizers. Repeated St. John's wort administration did not affect the CYP1A2 phenotypic ratio for both CYP2C19 genotype subjects. In conclusion, St. John's wort is an inducer to the human CYP2C19, and clinicians should pay great attention when St. John's wort is added to or withdrawn from an existing drug regimen containing substrates for such enzymes.
- Published
- 2004
16. Arg257Cys polymorphism of CYP2A13 in a Chinese population
- Author
-
Gan Zhou, Wei-Xia Zhang, Hong-Hao Zhou, Dan Wang, Guo-Lin Chen, and Xin-Yuan Cheng
- Subjects
Adult ,Male ,Adolescent ,Genotype ,Clinical Biochemistry ,Single-nucleotide polymorphism ,Biology ,Arginine ,Polymerase Chain Reaction ,Biochemistry ,law.invention ,Exon ,Asian People ,Gene Frequency ,law ,Humans ,Cysteine ,Allele ,Allele frequency ,Alleles ,Polymerase chain reaction ,Genetics ,Polymorphism, Genetic ,Biochemistry (medical) ,Heterozygote advantage ,General Medicine ,CYP2A13 ,Female ,Aryl Hydrocarbon Hydroxylases - Abstract
Background: Human cytochrome P450 2A13 (CYP2A13) is involved in the activation of numerous toxicants and carcinogens, especially in the metabolic activation of 4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a major tobacco-specific carcinogen. A functionally significant coding single nucleotide polymorphism (C3375T) in exon 5 of CYP2A13, which results in an amino acid substitution of Arg 257 to Cys, has been recently reported to exist in White, Black, Hispanic, and Asian individuals, with the variant 3375T allele frequencies being 1.9%, 14.4%, 5.8% and 7.7%, respectively. Since genetic background differs between ethnic groups, our present study aims to characterize the CYP2A13 Arg257Cys polymorphism in Chinese. Methods: 258 healthy Chinese Han volunteers were involved in this study. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay was employed to genotype for the Arg257Cys polymorphism. Results: Of all the 258 subjects, 27 (10.5%) heterozygotes and 1 (0.4%) homozygote for the 257Cys allele were detected. The frequency of the variant 257Cys allele in this Chinese population was 5.6% (95%CI: 4.2–7.0%). Conclusion: The CYP2A13 Arg257Cys variant represents a common polymorphism in Chinese, with the 257Cys allele frequency being similar to the Hispanic and Asian groups, but significantly lower than the Black. D 2004 Published by Elsevier B.V.
- Published
- 2004
17. Genotype–phenotype correlation for histamine N-methyltransferase in a Chinese Han population
- Author
-
Zhen-Hua Xu, Hong Hao Zhou, Guo-Lin Chen, Wei Wang, Gan Zhou, Lian Sheng Wang, Bing Zhu, and Dan Wang
- Subjects
Adult ,Male ,China ,Histamine N-Methyltransferase ,Erythrocytes ,Methyltransferase ,Adolescent ,Genotype ,Clinical Biochemistry ,Population ,Biology ,Polymorphism, Single Nucleotide ,Biochemistry ,Genetic analysis ,chemistry.chemical_compound ,Humans ,SNP ,education ,Gene ,education.field_of_study ,Histamine N-methyltransferase ,Reverse Transcriptase Polymerase Chain Reaction ,Biochemistry (medical) ,General Medicine ,Molecular biology ,Phenotype ,chemistry ,Female ,Polymorphism, Restriction Fragment Length ,Histamine - Abstract
Two potential single-nucleotide polymorphisms (SNP) (C314T and A595G) exist in the gene for human histamine N-methyltransferase (HNMT).A radiochemical microassay was used to measure the erythrocyte HNMT activities, whereas the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was employed to perform the genetic analysis in 247 unrelated Chinese Han subjects.All subjects had detectable HNMT activity. The activity of HNMT was gender related (malesfemales, p0.0001), with a 5.5-fold individual variation. The distribution of HNMT activity was compatible with a normal distribution. There were 28 heterozygotes for the variant T314 allele among the 247 subjects, whereas no A595G transition was observed. All heterozygotes for the T314 allele displayed an intermediate or low HNMT activity, with an average HNMT activity being 34.0% lower than those with wild-type genotype (623.1+/-136.0 vs. 944.8+/-249.3 U/ml red blood cells [RBC], p0.0001).The C314T polymorphism was functionally important and contributes in part to phenotypic variance of HNMT activity in Chinese Han population. Additional unknown genetic or epigenetic factors should also play important roles in the regulation of HNMT activity.
- Published
- 2003
18. Histamine N-methyltransferase gene polymorphisms in Chinese and their relationship with enzyme activity in erythrocytes
- Author
-
Haijian Wang, Guo-Lin Chen, Wei Wang, Fuchu He, Gan Zhou, Zhen-Hua Xu, and Hong-Hao Zhou
- Subjects
Adult ,Male ,Untranslated region ,China ,Histamine N-Methyltransferase ,Linkage disequilibrium ,Erythrocytes ,Adolescent ,5' Flanking Region ,5' flanking region ,Single-nucleotide polymorphism ,Biology ,Polymorphism, Single Nucleotide ,Linkage Disequilibrium ,White People ,Sex Factors ,Asian People ,Gene Frequency ,Genetics ,Humans ,Genetic Testing ,General Pharmacology, Toxicology and Pharmaceutics ,Allele ,3' Untranslated Regions ,Allele frequency ,Alleles ,Polymorphism, Genetic ,Histamine N-methyltransferase ,Haplotype ,Genetic Variation ,Molecular biology ,Haplotypes ,Female ,Polymorphism, Restriction Fragment Length - Abstract
The aim of this study was to identify polymorphisms in the histamine N-methyltransferase (HNMT) gene in Chinese and to assess their relationship with HNMT activity. One hundred and ninety-two unrelated subjects were recruited. HNMT polymorphisms were screened by direct sequencing with purified polymerase chain reaction products comprising all six exons, plus splice junctions, as well as approximately 2 kb of the 5'-flanking region (5'-FR). Erythrocyte HNMT activity was previously measured by radiochemical microassay. A total of 11 single nucleotide polymorphisms (SNPs) were identified, among which six SNPs had variant allele frequencies greater than 5%. Of the six common SNPs, three (-1637T>C, -463T>C and -411C>T) were located in 5'-FR, one (314C>T) in coding exons, and two (939A>G and 1097A>T) in the 3'-untranslated region (3'-UTR). Most of these common SNPs were in linkage disequilibrium. Genotype-phenotype correlation analyses were performed for those common SNPs in 5'-FR and 3'-UTR. In males, no significant association was found between HNMT activity and these non-coding SNPs. However, in females, the -1637T>C or -463T>C tended to be associated with decreased HNMT activity, whereas the 939A>G or 1097A>T appeared to be correlated with increased enzymatic activity. HNMT polymorphisms differ considerably between Chinese and American. The common SNPs in 5'-FR (-1637T>C and -463T>C) and 3'-UTR (939A>G and 1097A>T) might conditionally regulate the activity of HNMT, or might be genetically linked to unknown mutation(s) underlying the HNMT phenotypic variance.
- Published
- 2003
19. Tryptophan Hydroxylase-2: An Emerging Therapeutic Target for Stress Disorders
- Author
-
Gregory M. Miller and Guo-Lin Chen
- Subjects
Gene isoform ,Gene Expression ,Pharmacology ,Biology ,Anxiety ,Tryptophan Hydroxylase ,Biochemistry ,Article ,Species Specificity ,Stress, Physiological ,Gene expression ,Animals ,Humans ,Molecular Targeted Therapy ,Neurons ,Fatigue Syndrome, Chronic ,Polymorphism, Genetic ,TPH2 ,Depression ,Stressor ,Tryptophan hydroxylase ,Circadian Rhythm ,Isoenzymes ,Antidepressant ,Serotonin ,Neuroscience ,Stress, Psychological ,Hormone - Abstract
Serotonin (5-HT) has been long recognized to modulate the stress response, and dysfunction of 5-HT has been implicated in numerous stress disorders. Accordingly, the 5-HT system has been targeted for the treatment of stress disorders. Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in 5-HT synthesis, and the recent identification of a second, neuron-specific TPH isoform (TPH2) opened up a new area of research. With a decade of extensive investigation, it is now recognized that: (1) TPH2 exhibits a highly flexible gene expression that is modulated by an increasing number of internal and external environmental factors including the biological clock, stressors, endogenous hormones, and antidepressant therapies; and (2) genetically determined TPH2 activity is linked to a growing body of stress-related neuronal correlates and behavioral traits. These findings reveal an active role of TPH2 in the stress response and provide new insights into the long recognized but not yet fully understood 5-HT-stress interaction. As a major modulator of 5-HT neurotransmission and the stress response, TPH2 is of both pathophysiological and pharmacological significance, and is emerging as a new therapeutic target for the treatment of stress disorders. Given that numerous antidepressant therapies influence TPH2 gene expression, TPH2 is already inadvertently targeted for the treatment of stress disorders. With increased understanding of the regulation of TPH2 activity we can now purposely utilize TPH2 as a target to develop new or optimize current therapies, which are expected to greatly improve the prevention and treatment of a wide variety of stress disorders.
- Published
- 2013
20. Advances in Tryptophan Hydroxylase-2 Gene Expression Regulation: New Insights into Serotonin-Stress Interaction and Clinical Implications
- Author
-
Guo-Lin Chen and Gregory M. Miller
- Subjects
Cortisol secretion ,Gene isoform ,Regulation of gene expression ,medicine.medical_specialty ,endocrine system ,Serotonin ,TPH2 ,Mental Disorders ,Pituitary-Adrenal System ,Biology ,Tryptophan hydroxylase ,Tryptophan Hydroxylase ,Article ,Cellular and Molecular Neuroscience ,Psychiatry and Mental health ,Endocrinology ,Phenotype ,Gene Expression Regulation ,Internal medicine ,Gene expression ,medicine ,Humans ,Epigenetics ,Genetics (clinical) - Abstract
Serotonin (5-HT) modulates the stress response by interacting with the hormonal hypothalamic-pituitary-adrenal (HPA) axis and neuronal sympathetic nervous system (SNS). Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in 5-HT biosynthesis, and the recent identification of a second, neuron-specific TPH isoform (TPH2) opened up a new area of research. While TPH2 genetic variance has been linked to numerous behavioral traits and disorders, findings on TPH2 gene expression have not only reinforced, but also provided new insights into, the long-recognized but not yet fully understood 5-HT-stress interaction. In this review, we summarize advances in TPH2 expression regulation and its relevance to the stress response and clinical implications. Particularly, based on findings on rhesus monkey TPH2 genetics and other relevant literature, we propose that: (i) upon activation of adrenal cortisol secretion, the cortisol surge induces TPH2 expression and de novo 5-HT synthesis; (ii) the induced 5-HT in turn inhibits cortisol secretion by modulating the adrenal sensitivity to ACTH via the suprachiasmatic nuclei (SCN)-SNS-adrenal system, such that it contributes to the feedback inhibition of cortisol production; (iii) basal TPH2 expression or 5-HT synthesis, as well as early-life experience, influence basal cortisol primarily via the hormonal HPA axis; and (iv) 5'- and 3'-regulatory polymorphisms of TPH2 may differentially influence the stress response, presumably due to their differential roles in gene expression regulation. Our increasing knowledge of TPH2 expression regulation not only helps us better understand the 5-HT-stress interaction and the pathophysiology of neuropsychiatric disorders, but also provides new strategies for the treatment of stress-associated diseases.
- Published
- 2012
21. Normal thermoregulatory responses to 3-iodothyronamine, trace amines and amphetamine-like psychostimulants in trace amine associated receptor 1 knockout mice
- Author
-
Thomas S. Scanlan, Spencer K. Lynn, Helen N. Panas, Eric J. Vallender, Laurie J. Lynch, Zhihua Xie, Gregory M. Miller, and Guo-Lin Chen
- Subjects
Agonist ,Male ,medicine.medical_specialty ,Serotonin ,Thyroid Hormones ,Serotonin uptake ,medicine.drug_class ,Dopamine ,N-Methyl-3,4-methylenedioxyamphetamine ,Pharmacology ,Article ,Cell Line ,Methamphetamine ,Receptors, G-Protein-Coupled ,3-Iodothyronamine ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,Mice ,Internal medicine ,TAAR1 ,Phenethylamines ,medicine ,Thyronines ,Animals ,Humans ,Amphetamine ,Dopamine transporter ,Mice, Knockout ,Dopamine Plasma Membrane Transport Proteins ,biology ,Macaca mulatta ,Corpus Striatum ,Endocrinology ,Monoamine neurotransmitter ,chemistry ,biology.protein ,Central Nervous System Stimulants ,medicine.drug ,Body Temperature Regulation ,Synaptosomes - Abstract
3-Iodothyronamine (T1AM) is a metabolite of thyroid hormone. It is an agonist at trace amine-associated receptor 1 (TAAR1), a recently identified receptor involved in monoaminergic regulation and a potential novel therapeutic target. Here, T1AM was studied using rhesus monkey TAAR1 and/or human dopamine transporter (DAT) co-transfected cells, and wild-type (WT) and TAAR1 knock-out (KO) mice. The IC(50) of T1AM competition for binding of the DAT-specific radio-ligand [(3)H]CFT was highly similar in DAT cells, WT striatal synaptosomes and KO striatal synaptosomes (0.72-0.81 microM). T1AM inhibition of 10 nM [(3)H]dopamine uptake (IC(50): WT, 1.4 + or - 0.5 microM; KO, 1.2 + or - 0.4 microM) or 50 nM [(3)H]serotonin uptake (IC(50): WT, 4.5 + or - 0.6 microM; KO, 4.7 + or - 1.1 microM) in WT and KO synaptosomes was also highly similar. Unlike other TAAR1 agonists that are DAT substrates, TAAR1 signaling in response to T1AM was not enhanced in the presence of DAT as determined by CRE-luciferase assay. In vivo, T1AM induced robust hypothermia in WT and KO mice equivalently and dose dependently (maximum change degrees Celsius: 50 mg/kg at 60 min: WT -6.0 + or - 0.4, KO -5.6 + or - 1.0; and 25 mg/kg at 30 min: WT -2.7 + or - 0.4, KO -3.0 + or - 0.2). Other TAAR1 agonists including beta-phenylethylamine (beta-PEA), MDMA (3,4-methylenedioxymethamphetamine) and methamphetamine also induced significant, time-dependent thermoregulatory responses that were alike in WT and KO mice. Therefore, TAAR1 co-expression does not alter T1AM binding to DAT in vitro nor T1AM inhibition of [(3)H]monoamine uptake ex vivo, and TAAR1 agonist-induced thermoregulatory responses are TAAR1-independent. Accordingly, TAAR1-directed compounds will likely not affect thermoregulation nor are they likely to be cryogens.
- Published
- 2010
22. TPH2 5'- and 3'-regulatory polymorphisms are differentially associated with HPA axis function and self-injurious behavior in rhesus monkeys
- Author
-
Melinda A. Novak, Jerrold S. Meyer, Gregory M. Miller, Brian J. Kelly, Eric J. Vallender, and Guo-Lin Chen
- Subjects
Male ,medicine.medical_specialty ,Hypothalamo-Hypophyseal System ,Cortisol awakening response ,Genotype ,Hydrocortisone ,Radioimmunoassay ,Pituitary-Adrenal System ,Adrenocorticotropic hormone ,Biology ,Tryptophan Hydroxylase ,Article ,Cell Line ,Behavioral Neuroscience ,Adrenocorticotropic Hormone ,Gene Frequency ,Internal medicine ,Genetics ,medicine ,Animals ,Humans ,Allele frequency ,Cells, Cultured ,Analysis of Variance ,Polymorphism, Genetic ,TPH2 ,Behavior, Animal ,Haplotype ,Macaca mulatta ,Rats ,Endocrinology ,Phenotype ,Neurology ,Haplotypes ,Serotonin ,Self-Injurious Behavior ,medicine.drug - Abstract
Tryptophan hydroxylase-2 (TPH2) synthesizes neuronal serotonin and is linked to numerous behavioral traits. We have previously characterized the functionality of polymorphisms (especially 2051A>C) in 3’-untranslated region (3’-UTR) of rhesus monkey TPH2 (rhTPH2). This study further assessed the functionality of additional polymorphisms (–1605T>C, –1491Tn, –1485(AT)n, –1454A>G, –1325In>Del and –363T>G) in rhTPH2 5’-flanking region (5’-FR), and evaluated the effects of rhTPH2 5’ and 3’ genotypes on central serotonin turnover, hypothalamic–pituitary–adrenal (HPA) axis function and self-injurious behavior (SIB) in 32 unrelated adult male monkeys of Indian origin. Haplotypes of the rhTPH2 5’-FR polymorphisms exert a significant, cell-dependent effect on reporter gene expression, primarily conferred by –1485(AT)n. The –1485(AT)n and 2051A>C polymorphisms interact to influence cerebrospinal fluid (CSF) 5-HIAA and plasma adrenocorticotropic hormone (ACTH) in the afternoon. While –1485(AT)n exerts significant main effects on the afternoon cortisol level and nocturnal HPA negative feedback, 2051A>C has significant main effects on the morning cortisol level and cortisol response to ACTH challenge, as well as marginally significant main effects on the daytime HPA negative feedback and self-biting rate. In addition, the genotype/allele frequency of the 5’-FR –1325Ins>Del differed significantly between the self-wounders and non-wounders, whereas 3’-UTR 2128S>L polymorphism differed significantly in genotype/allele frequency between the high- and low-frequency biters. This study shows the functionality of rhTPH2 5’-FR polymorphisms, and provides evidence for the differential association of rhTPH2 5’-FR and 3’-UTR polymorphisms with HPA axis function and SIB. Our findings shed light on the role of TPH2 gene variance in physiology and behavioral traits, and also contribute to the understanding of the pathophysiology and genetics of SIB
- Published
- 2010
23. [Herbs for calming liver and suppressing liver-yang in treatment of migraine with hyperactive liver-yang syndrome and its effects on lymphocyte protein expression: a randomized controlled trial]
- Author
-
Yan-hong Luo, Yao-hui Yin, Zhen-jia Yi, Wei Li, Guangwei Zhong, Ying Zhang, Le Zhang, Guo-lin Chen, and Jian-jun Hu
- Subjects
Adult ,Male ,Proteomics ,Low protein ,Adolescent ,Proteome ,Lymphocyte ,Migraine Disorders ,Peroxiredoxin 2 ,Traditional Chinese medicine ,Pharmacology ,law.invention ,Young Adult ,Randomized controlled trial ,law ,medicine ,Humans ,Yin-Yang ,Lymphocytes ,Medicine, Chinese Traditional ,Flunarizine ,Aged ,business.industry ,Therapeutic effect ,Middle Aged ,medicine.disease ,medicine.anatomical_structure ,Complementary and alternative medicine ,Migraine ,Female ,business ,medicine.drug ,Drugs, Chinese Herbal ,Phytotherapy - Abstract
OBJECTIVE To observe the efficacy of herbs for calming liver and suppressing liver-yang in treatment of migraine patients with hyperactivity of liver-yang syndrome and to investigate its effects on the lymphocyte protein expression. This approach may lay a foundation for the further investigation of pathogenic mechanisms in migraine with hyperactive liver-yang syndrome and the curative mechanisms of calming liver and suppressing liver-yang treatment. METHODS A total of 32 migraine patients with hyperactivity of liver-yang syndrome were randomly divided into treatment group (16 cases) and control group (16 cases). The patients in the treatment group were treated with herbs for calming liver and suppressing liver-yang in accordance with traditional Chinese medicine (TCM) theory and the patients in the control group were treated with Flunarizine Capsules for two courses of treatment. The therapeutic effects, the score of TCM symptom and the changes of headache attack were observed in both groups before and after the treatment. The side effects were also observed in both groups. The level of differential protein expression was analyzed by two-dimensional electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). RESULTS The herbs for calming liver and suppressing liver-yang had better effects on headache improvement than the Flunarizine Capsules (P
- Published
- 2009
24. [Effect of calming the liver and suppressing the hyperactive YANG drugs on lymphocyte protein in hypertension patients with hyperactivity of liver-YANG]
- Author
-
Guang-wei, Zhong, Wei, Li, Yan-hong, Luo, Guo-lin, Chen, Zhen-jia, Yi, Ze-qi, Chen, Chen, Zhang, and Chuan-man, Peng
- Subjects
Adult ,Male ,Proteins ,Middle Aged ,Diagnosis, Differential ,Hypertension ,Humans ,Yin-Yang ,Electrophoresis, Gel, Two-Dimensional ,Female ,Lymphocytes ,Medicine, Chinese Traditional ,Aged ,Drugs, Chinese Herbal ,Phytotherapy - Abstract
To explore the effect of calming the liver and suppressing the hyperactive YANG drugs on the lymphocyte protein and clinical efficacy in the hypertension patients with hyperactivity of liver-YANG, and to identify the therapy.Twenty-six hypertension patients with hyperactivity of liver-YANG were treated by calming the liver and suppressing the hyperactive YANG drugs for 2 courses. Symptoms of Chinese medicine and blood pressure were observed, and the separated lymphocyte total protein of normal and hypertensions before and after the treatment were examined by the solid-state pH gradient 2-dimensional gel electrophoresis. The differences of the protein expression were analyzed by ImageMaster 2DE analysis software with two-way patterns.The total efficiency rate of calming the liver and suppressing the hyperactive YANG drugs was 88.5%, and the drugs could significantly relieve the symptoms, such as headache, dizziness, dry mouth, irritability, etc. Calming the liver and suppressing the hyperactive YANG drugs could also remarkably reduce the blood pressure,with significant different between pre-treatment and post-treatment (P0.05). The average spots of lymphocyte gel proteins in the normal and the hypertension patients with syndrome of hyperactivity of liver-YANG before and after the treatment were 527+/-41,559+/-62, and 543+/-59, respectively. Compared with normal people, the expression of 15 proteins was down-regulated, and 10 up-regulated in the hypertension patients with syndrome of hyperactivity of liver-YANG. Compared with the pre-treatment, the expression of 12 proteins was increased in the 15 down-regulated proteins, and 6 decreased in the 10 up-regulated proteins after the treatment in the hypertension patients with syndrome of the hyperactivity of liver-YANG.Calming the liver and suppressing the hyperactive yang drugs may mildly depress the blood pressure and improve the symptoms of Chinese medicine. The effect of drugs in treating hypertension may probably be associated with regulating the expression of some proteins in lymphocytes.
- Published
- 2008
25. Functional variation in the 3' untranslated region of the serotonin transporter in human and rhesus macaque
- Author
-
S. Hakim, Guo-Lin Chen, Hong Yang, Eric J. Vallender, Gregory M. Miller, and C. M. Priddy
- Subjects
Untranslated region ,Serotonin ,RNA Stability ,Population ,DNA Mutational Analysis ,Single-nucleotide polymorphism ,Polymorphism, Single Nucleotide ,Behavioral Neuroscience ,Species Specificity ,Genes, Reporter ,Neural Pathways ,Genetics ,Animals ,Humans ,Genetic Testing ,Allele ,Selection, Genetic ,education ,Gene ,3' Untranslated Regions ,Serotonin transporter ,Brain Chemistry ,Serotonin Plasma Membrane Transport Proteins ,education.field_of_study ,biology ,Three prime untranslated region ,Brain ,Genetic Variation ,Hominidae ,biology.organism_classification ,Macaca mulatta ,Rhesus macaque ,Neurology ,Gene Expression Regulation ,Haplotypes ,biology.protein - Abstract
The serotonin system underlies a wide variety of behavioral traits and its dysregulation is the cause of numerous neuropsychiatric disorders. Among genes involved in the system, the serotonin transporter (SERT) is integral and has been repeatedly shown to be associated with disease as well as being a primary drug target. In addition to promoter region variation, we identify here variation in a regulatory region in the 3′ untranslated region (UTR) of the SERT gene in both humans and rhesus macaques. We comprehensively survey the 3′ UTR of SLC6A4 in Indian-origin rhesus macaques to identify three single nucleotide polymorphisms (SNPs) creating two haplotypes, both derived from an ancestral sequence, that represent the vast majority of the alleles in the population. Through the use of a luciferase reporter gene assay, we are able to show that not only do these alleles have differential effects on gene expression, modulated through changes in messenger RNA stability, but that different commonly occurring SNPs in the human 3′ UTR also have similar effects. This finding not only offers additional insight into the regulation, and thus dysregulation, of SERT expression, but also suggests the role of natural selection in maintaining both high and low SERT expression levels broadly across populations of multiple primate species.
- Published
- 2008
26. Human expression variation in the mu-opioid receptor is paralleled in rhesus macaque
- Author
-
Guo-Lin Chen, Cassandra M. Priddy, Eric J. Vallender, and Gregory M. Miller
- Subjects
Linkage disequilibrium ,medicine.drug_class ,Receptors, Opioid, mu ,Polymorphism, Single Nucleotide ,Gene Frequency ,Species Specificity ,Opioid receptor ,Polymorphism (computer science) ,biology.animal ,Genetic variation ,Genetics ,medicine ,Animals ,Humans ,Primate ,Genetics (clinical) ,Ecology, Evolution, Behavior and Systematics ,Polymorphism, Genetic ,biology ,Haplotype ,Genetic Variation ,DNA ,biology.organism_classification ,Phenotype ,Macaca mulatta ,Rhesus macaque - Abstract
The mu-opioid receptor is a key component in many neurobiological systems including those affecting perceptions of pain and pleasure. In humans and non-human primate model systems, genetic variation in the receptor has been associated with numerous behavioral and physiological traits. In humans, polymorphisms have been identified which affect not only the biochemical function of the receptor, but also expression level. Existing rhesus macaque variation parallels the functional protein changes seen in human, but it remains unknown if expression level differences or concomitant protein changes may also exist. Here we perform a comprehensive survey of naturally occurring polymorphisms in Indian-origin rhesus macaques and identify three 5′ UTR haplotypes with effects on expression level. These expression level effects are in linkage disequilibrium with the previously identified rhesus coding polymorphism C77G. The C77G polymorphism in rhesus parallels the functional effects of the A118G polymorphism in humans and expression level differences occur within both species. Together, the functional variations reported here have implications for future studies seeking to model the opioid system and its associated phenotypes in rhesus macaques.
- Published
- 2007
27. [Immune response to HSP70-HBcAg(18-27) complex in HBV transgenic mice]
- Author
-
Huai-dong, Hu, Peng, Hu, Guo-lin, Chen, Ming-li, Peng, Min, Chen, and Hong, Ren
- Subjects
Male ,Hepatitis B virus ,Mice ,Animals ,Female ,HSP70 Heat-Shock Proteins ,Mice, Transgenic ,Hepatitis B Core Antigens ,Spleen ,T-Lymphocytes, Cytotoxic - Abstract
To study the cellular immune response to HSP70-HBcAg(18-27) complex in HBV transgenic mice.HSP70-HBcAg(18-27) complex was reconstituted in vitro, then it was injected into HBV transgenic mice to observe the cellular immune response. At the same time, we investigated whether HSP70-HBcAg(18-27) complex could generate antigen specific cytotoxic T lymphocyte responses in spleen cells.Our results demonstrated that HSP70-HBcAg(18-27) complex increased levels of CD4+ and CD8+ T cells in the spleens and peripheral blood of HBV transgenic mice, and the complex also activated dendritic and natural killer cells.HSP70-HBcAg(18-27) complex has an immunological antigenicity in raising the immunoresponse to chronic HBV infection in HBV transgenic mice. HSP70-HBcAg(18-27) complex might be considered as a candidate for further studies on its role as a therapeutic vaccine against chronic HBV infection in humans.
- Published
- 2007
28. Balancing selection and the evolution of functional polymorphism in Old World monkey TRIM5alpha
- Author
-
Ruchi M. Newman, Welkin E. Johnson, Guo-Lin Chen, Amitinder Kaur, Laura R. Hall, Gregory M. Miller, Eloísa Yuste, Shuji Sato, Eric Hunter, William E. Diehl, and Michelle Connole
- Subjects
Nonsynonymous substitution ,Molecular Sequence Data ,Locus (genetics) ,Old World monkey ,Balancing selection ,Major histocompatibility complex ,Evolution, Molecular ,Phylogenetics ,biology.animal ,Animals ,Humans ,Primate ,Amino Acid Sequence ,Allele ,Selection, Genetic ,Alleles ,Cells, Cultured ,Phylogeny ,Genetics ,Multidisciplinary ,Polymorphism, Genetic ,biology ,Cercopithecidae ,Biological Sciences ,biology.organism_classification ,Evolutionary biology ,Multigene Family ,biology.protein ,Cats ,Carrier Proteins - Abstract
Retroviral restriction factor TRIM5α exhibits a high degree of sequence variation among primate species. It has been proposed that this diversity is the cumulative result of ancient, lineage-specific episodes of positive selection. Here, we describe the contribution of within-species variation to the evolution of TRIM5α. Sampling within two geographically distinct Old World monkey species revealed extensive polymorphism, including individual polymorphisms that predate speciation (shared polymorphism). In some instances, alleles were more closely related to orthologues of other species than to one another. Both silent and nonsynonymous changes clustered in two domains. Functional assays revealed consequences of polymorphism, including differential restriction of a small panel of retroviruses by very similar alleles. Together, these features indicate that the primate TRIM5α locus has evolved under balancing selection. Except for the MHC there are few, if any, examples of long-term balancing selection in primates. Our results suggest a complex evolutionary scenario, in which fixation of lineage-specific adaptations is superimposed on a subset of critical polymorphisms that predate speciation events and have been maintained by balancing selection for millions of years.
- Published
- 2006
29. [Effect of tumor antigen specific CTL induced by dendritic cells on a model of human hepatocellular carcinoma in nude mice (LCI-D20)]
- Author
-
Guo-lin, Chen, Huai-dong, Hu, Ying-ji, Ma, Yong-guo, Li, Qiong, Xue, Min, Chen, and Hong, Ren
- Subjects
Male ,Carcinoma, Hepatocellular ,Liver Neoplasms ,Granulocyte-Macrophage Colony-Stimulating Factor ,Mice, Nude ,Dendritic Cells ,Recombinant Proteins ,Mice ,Antigens, Neoplasm ,Cell Line, Tumor ,Animals ,Interleukin-4 ,Neoplasm Metastasis ,Neoplasm Transplantation ,T-Lymphocytes, Cytotoxic - Abstract
To investigate the cure effect of tumor antigen specific CTL on a model of human hepatocellular carcinoma in nude mice LCI-D20.Dendritic cells (DCs) were induced from peripheral blood mononuclear cells of healthy people in vitro by using recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) and interleukin-4 (rhIL-4) and were pulsed with tumor antigen from hepatocellular carcinoma cell line MHCC97H. Then tumor antigen specific cytotoxic T lymphocytes (CTLs) were induced. By intraperitoneal injection of tumour antigen specific CTLs into the LCI-D20, the preventive and therapeutic effects of these CTLs to HCC in the LCI-D20 model were assessed. Cytokine-induced killer (CIK) cells and phosphate buffer solution were used as controls at the same time.The weights of tumors in the tumor antigen specific CTL group, in the CIK cell group and in the blank group were (1.11+/-0.63), (1.12+/-0.36) and (2.68+/-0.53) grams respectively (t = 5.18, t = 6.06, P0.01). The amount of blood alpha fetal protein in the tumor antigen specific CTL and CIK groups were (52.1+/-9.7) microg/L and (48.6+/-5.2) microg/L, and was (82.2+/-7.2) microg/L in the blank group (t = 17.26, t = 22.07, P0.01 respectively). The metastasis rates in livers were 16.7%, 16.7% and 58.3% in the tumor antigen specific CTL, CIK cell and blank control groups respectively (chi2= 4.44, P0.01). The survival time of the mice in the tumor antigen specific CTL group was (79.0+/-5.02) days, (73.3+/-7.0) days in the CIK group, and (52.3+/-5.2) days in the blank group (t = 14.56, t = 17.54, P0.01).Tumor antigen specific CTLs may prevent metastasis in the LCI-D20 model and prolong the survival time.
- Published
- 2006
30. Gender specific association of CYP2C9*3 with hyperlipidaemia in Chinese
- Author
-
Wei-Xia Zhang, Bang-Ning Yu, A. M. Abd El-Aty, Guo-Lin Chen, Xiao-Hong Duan, Wei Mo, Hong-Hao Zhou, Chen-Hui Luo, Dong-Sheng Ouyang, An Wang, and Rong-Hua Zhu
- Subjects
Adult ,Male ,medicine.medical_specialty ,China ,Genotype ,Female group ,Hyperlipidemias ,Total population ,Biology ,Gastroenterology ,Polymerase Chain Reaction ,Asian People ,Gene Frequency ,Internal medicine ,Hyperlipidemia ,medicine ,Humans ,Pharmacology (medical) ,In patient ,Genetic Predisposition to Disease ,Allele frequency ,Aged ,Cytochrome P-450 CYP2C9 ,Pharmacology ,Sex Characteristics ,Middle Aged ,medicine.disease ,CYP2C9*3 ,Endocrinology ,Pharmacogenetics ,biology.protein ,Female ,Aryl Hydrocarbon Hydroxylases ,Polymorphism, Restriction Fragment Length ,Sex characteristics - Abstract
To investigate the association of CYP2C9*3 and *6 with hyperlipidaemia in Chinese.Four hundred and seventy-six Chinese participated in the study, including 211 uncomplicated hyperlipidaemic patients and 265 healthy controls. PCR-RFLP was used to identify CYP2C9*3 and *6.CYP2C9*6 was not detected in this study. The allelic frequency of CYP2C9*3 was 0.039 (95% CI 0.022, 0.056). A nonsignificant difference existed in CYP2C9*3 frequencies between males and females (P = 0.605, OR = 1.194, 95% CI 0.610, 2.336), patients and controls (P = 0.063, OR = 0.506, 95% CI 0.244, 1.049) in the total population. However, in the female group, CYP2C9*3 frequency in patients with hyperlipidaemia was significantly lower than that in controls (P0.0001, OR = 0.062, 95% CI 0.008, 0.476).The association of CYP2C9*3 with hyperlipidaemia was specific for females in this Chinese population.
- Published
- 2005
31. Single nucleotide polymorphisms and haplotypes of histamine N-methyltransferase in patients with gastric ulcer
- Author
-
Jianshe Liu, Zhen-Hua Xu, Guo-Lin Chen, Zhi-Rong Tan, Wei Wang, W. P. Nie, Hong Hao Zhou, Gan Zhou, and Bing Zhu
- Subjects
Adult ,Male ,Allergy ,Histamine N-Methyltransferase ,Adolescent ,Genotype ,Immunology ,Single-nucleotide polymorphism ,Pharmacology ,Polymerase Chain Reaction ,Polymorphism, Single Nucleotide ,Pathogenesis ,chemistry.chemical_compound ,Medicine ,Humans ,Secretion ,Genetic Predisposition to Disease ,Stomach Ulcer ,Aged ,chemistry.chemical_classification ,Histamine N-methyltransferase ,business.industry ,digestive, oral, and skin physiology ,Middle Aged ,medicine.disease ,digestive system diseases ,Enzyme ,Biochemistry ,chemistry ,Haplotypes ,Case-Control Studies ,Gastric acid ,Female ,business ,Histamine ,Polymorphism, Restriction Fragment Length - Abstract
Histamine plays a crucial role in the regulation of gastric acid secretion, which is involved in the pathogenesis of peptic ulcer. Histamine N-methyltransferase (HNMT) is the major metabolizing enzyme for histamine inactivation in human stomach.This study aims to determine whether there exists a relationship between HNMT gene polymorphisms and the risk for gastric ulcer (GU).118 GU patients and 154 ethnically matched control subjects were enrolled and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assays were developed to genotype all these subjects for the T-1637C, C-411T, C314T and A1097T point mutations in HNMT gene. Haplotypes were reconstructed from the genotype data.Frequencies of the variant alleles in cases and controls were 0.398 vs 0.396 for T-1637C, 0.144 vs 0.110 for C-411T, 0.034 vs 0.042 for C314T, and 0.242 vs 0.273 for A1097T, respectively, with no significant difference for any locus between the two groups (all P0.05). Also the frequencies of genotypes, haplotypes and haplotype pairs based on these polymorphisms did not differ significantly between cases and controls.This study provided no evidence for the involvement of HNMT polymorphisms in the susceptibility to GU.
- Published
- 2004
32. CYP3A5*3 and CYP3A4*18 single nucleotide polymorphisms in a Chinese population
- Author
-
Li-Fang Duan, Jun He, Zhong-Qi Liu, Che Zhang, Guo-Lin Chen, Dan Wang, Yong-Fang Hu, and Hong-Hao Zhou
- Subjects
Adult ,Male ,China ,Adolescent ,CYP3A ,Clinical Biochemistry ,Single-nucleotide polymorphism ,Biochemistry ,Polymerase Chain Reaction ,Polymorphism, Single Nucleotide ,Cytochrome P-450 Enzyme System ,Genotype ,Cytochrome P-450 CYP3A ,Humans ,Allele ,CYP3A5 ,Allele frequency ,Alleles ,Genetics ,biology ,CYP3A4 ,Biochemistry (medical) ,Cytochrome P450 ,General Medicine ,biology.protein ,Polymorphism, Restriction Fragment Length - Abstract
Background: Human cytochrome P450 3A evolved to catalyze the metabolism of numerous common therapy drugs and endogenous molecules. Members of the CYP3A are the majority expressed in human liver and intestine, and there are marked interindividual differences in their protein expression and activity. The activity of CYP3A enzyme in Chinese is highly variable, exceeding 14-fold, and contributes greatly to variation in oral bioavailability and systemic clearance of CYP3A substrates. The genetic factors play an important role in the interindividual variability in CYP3A activity. Detection of CYP3A5 and CYP3A4 variant alleles and knowledge about their allelic frequency in specific ethnic groups are important to lead to individualized drug dosing and improved therapeutics. Methods: We determined the allelic frequency of the CYP3A5*3 and CYP3A4*18 in a group of 302 Chinese subjects by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assays. Results: In the group of 302 unrelated individuals, the frequency of the CYP3A5*3 and CYP3A4*18 variant allele in Chinese population were 0.778 (95% CI: 0.754, 0.802) and 0.01 (95% CI: 0, 0.02), respectively. Conclusions: We developed a simple assay for the detection of the CYP3A4*18 allele and showed that in a Chinese population, CYP3A4*18 and CYP3A5*3 allelic frequencies are similar to that reported previously in Chinese resident in Taiwan. The frequency of the CYP3A5*3 allele in Chinese population is similar to the Japanese but lower than Caucasians. Meanwhile, our findings suggest that an approximate 62% of the Chinese population carrying CYP3A5*3/*3 genotype may appear not to express CYP3A5 protein. D 2004 Elsevier B.V. All rights reserved.
- Published
- 2004
33. Pharmacokinetics of citalopram in relation to genetic polymorphism of CYP2C19
- Author
-
Zhao-Qian Liu, Hong-Hao Zhou, Dong-Sheng Ouyang, Nan He, Guo-Lin Chen, Bang-Ning Yu, and Xiao-Ping Chen
- Subjects
Adult ,Male ,Desmethylcitalopram ,Genotype ,Cmax ,Pharmaceutical Science ,CYP2C19 ,Citalopram ,Pharmacology ,Biology ,behavioral disciplines and activities ,Mixed Function Oxygenases ,chemistry.chemical_compound ,Pharmacokinetics ,Asian People ,Oral administration ,mental disorders ,Blood plasma ,medicine ,Humans ,Polymorphism, Genetic ,CYP3A4 ,Cytochrome P-450 CYP2C19 ,chemistry ,Aryl Hydrocarbon Hydroxylases ,medicine.drug - Abstract
The study was designed to define the contribution of cytochrome p450 2C19 (CYP2C19) and cytochrome p450 3A4 (CYP3A4) to citalopram N-demethylation and to evaluate the relationship between the disposition of citalopram and CYP2C19 genotype. A single oral 40-mg dose of citalopram was administered to eight extensive metabolizers and five poor metabolizers recruited from 77 healthy Chinese volunteers whose genotypes and phenotypes were predetermined. The plasma concentrations of citalopram and desmethylcitalopram were determined by high-performance liquid chromatography. It was found that the genotype of CYP2C19 had a significant effect on the N-demethylation of citalopram. Poor metabolizers with m1 mutation had higher area under the plasma concentration versus time curve (AUC0--> infinity ) values than did extensive metabolizers. Terminal elimination half-life (t1/2) values of citalopram in poor metabolizers were significantly higher than the values in extensive metabolizers who were either homozygous or heterozygous with CYP2C19*1. The oral clearance (CLoral) of citalopram in poor metabolizers was significantly lower than that of extensive metabolizers. The AUC0--> infinity and maximum plasma concentration (Cmax) of desmethylcitalopram in poor metabolizers were significantly lower than the values of extensive metabolizers. The results show that CYP3A4 is not the major enzyme in the N-demethylation of citalopram among extensive metabolizers. The polymorphism of CYP2C19 plays an important role in the N- demethylation of citalopram in vivo. The extensive metabolizers and poor metabolizers of CYP2C19 had significant difference in disposition of citalopram in vivo.
- Published
- 2003
34. Evidence for the involvement of human liver microsomes CYP1A2 in the mono-hydroxylation of daidzein
- Author
-
A. M. Abd El-Aty, Guo-Lin Chen, Lian Sheng Wang, Wen Xing Peng, Hong Hao Zhou, and Huan De Li
- Subjects
Spectrometry, Mass, Electrospray Ionization ,Furafylline ,DNA, Complementary ,Cytochrome P-450 CYP1A2 Inhibitors ,Clinical Biochemistry ,In Vitro Techniques ,Hydroxylation ,Biochemistry ,chemistry.chemical_compound ,Cytochrome P-450 CYP1A2 ,Humans ,Estrogens, Non-Steroidal ,Enzyme Inhibitors ,Biotransformation ,Chromatography, High Pressure Liquid ,chemistry.chemical_classification ,CYP3A4 ,biology ,Chemistry ,Biochemistry (medical) ,Daidzein ,CYP1A2 ,Cytochrome P450 ,General Medicine ,Isoflavones ,Recombinant Proteins ,Isoenzymes ,Kinetics ,Enzyme ,biology.protein ,Microsome ,Microsomes, Liver ,Algorithms - Abstract
Background: In vitro studies with rats and human liver microsomes (HLM) demonstrated that daidzein is readily metabolized to mono-hydroxylated compounds. In this study, daidzein mono-hydroxylated metabolites was investigated using human liver microsomes to identify the cytochrome P450 (CYP) isoform(s) involved in this metabolic pathway. Methods: Kinetic analysis for the formation rates of mono-hydroxylated metabolites of daidzein, including 7,8,4′-trihydroxyisoflavone (7,8,4′-THI), 7,3,4′-trihydroxyisoflavone (7,3,4′-THI) and 6,7,4′-trihydroxyisoflavone (6,7,4′-THI), were performed using human liver microsomes (HLM) and recombinant enzymes at substrate concentrations ranging from 0.5 to 400 μmol/l. Nine selective inhibitors or substrate probes specific for different CYP isoforms were applied for screening the isoform(s) responsible for mono-hydroxylated metabolism of daidzein. Results: Michaelis–Menten kinetic parameters were best fitted to a one-component enzyme kinetic model. The mean Km (μmol/l) and Vmax (μmol/g min) values (±S.D.) were 26.86 (10.45) and 4.76 (2.07), 53.83 (22.25) and 2.29 (1.04), 51.48 (29.32) and 2.21(0.82), for the formation rates of 7,8,4′-THI, 7,3′,4′-THI and 6,7,4′-THI, respectively. Furafylline, the CYP1A2-specific inhibitor, estrogen and monoclonal antibody raised against human CYP1A2 (MAB-1A2) substantially inhibited the formation rates of mono-hydroxylated metabolites. The IC50 of Fur for the formation of 7,3′,4′-THI, 6,7,4′-THI and 7,8,4′-THI was 1.0, 0.9 and 0.8 μmol/l, respectively. The IC50 of estrogen for the formation of 7,3′,4′-THI, 6,7,4′-THI and 7,8,4′-THI was 51, 60 and 64 μmol/l, respectively. The IC50 of MAB-1A2 for the formation of the mono-hydroxylated products was 1 μmol/l, but neither other selective inhibitor nor substrate probes, including coumarin (CYP2D6), sulphaphenzole (CYP2C9/10), omeprazole (CYP2C19), quinidine (CYP2D6), diethyldithiocarbamate (CYP2E1), troleandomycin (CYP3A4) and keteconazole (CYP3A4), did so with human liver microsomes. Conclusion: Daidzein mono-hydroxylated products are principally metabolized by CYP1A2 in human.
- Published
- 2003
35. Analysis of the C314T and A595G mutations in histamine N-methyltransferase gene in a Chinese population
- Author
-
Guo-Lin Chen, Hong-Hao Zhou, Guang-ping Wang, Gan Zhou, Dan Wang, Zhen-Hua Xu, and Wei Wang
- Subjects
Adult ,Male ,Histamine N-Methyltransferase ,Genotype ,Clinical Biochemistry ,Population ,Biology ,Biochemistry ,Polymerase Chain Reaction ,Asian People ,Missense mutation ,Humans ,Point Mutation ,Allele ,education ,Allele frequency ,Alleles ,DNA Primers ,Genetics ,education.field_of_study ,Histamine N-methyltransferase ,Point mutation ,Biochemistry (medical) ,Heterozygote advantage ,General Medicine ,DNA ,Amino Acid Substitution ,Female ,Polymorphism, Restriction Fragment Length - Abstract
Background: Histamine N-methyltransferase (HNMT) plays an important role in the metabolism of histamine, a biogenic amine that has many physiologic and pathological roles in human tissues. A missense mutation C314T (Thr105Ile) in the HNMT gene has been identified to represent a common functional polymorphism in Caucasians, whereas an A595G (Ile199Val) variant has been reported in one HNMT cDNA from a Japanese subject. Methods: By using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay, the point mutations C314T and A595G within HNMT were both detected in 352 unrelated Chinese Han subjects. Results: None of the 352 subjects contained the A595G mutation, whereas 40 (11.6%) heterozygotes and 1 (0.3%) homozygote for the variant T314 allele were detected. The frequency of the variant T314 allele in this Chinese population was 0.060 (95% CI: 0.042–0.078), not different from Japanese but significantly lower than American Caucasians. Conclusions: The C314T mutation represents a common functional genetic polymorphism in the Chinese Han population with a variant T314 allele frequency similar to Japanese but lower than American Caucasians, whereas the A595G mutation does not appear to exist in this population.
- Published
- 2002
36. Plasma leucine enkephalin content in patients with (Liver-blood deficiency) syndrome and clinical significance
- Author
-
Yi-Gang Shu, Lin-Jie Shi, Wei-Hua Pang, Xue-Wen Li, Guo-Lin Chen, and Xiang Zhang
- Subjects
medicine.medical_specialty ,Pituitary gland ,Deficiency syndrome ,business.industry ,Gastroenterology ,Leucine-enkephalin ,General Medicine ,Iron deficiency ,Clinical Experience ,medicine.disease ,medicine.anatomical_structure ,Endocrinology ,Hypothalamus ,Internal medicine ,medicine ,In patient ,Clinical significance ,Aplastic anemia ,business - Abstract
Recent studies revealed that the leucine enkephalin (L-EK) was distributed in rat brains with a higher concentration in hypothalamus and little in the pituitary gland[1], but the study on the relationship of L-EK with “liver-blood deficiency” syndrome (LBDS) was lacking. We determined the plasma L-EK levels in LBDS patients with clinical features of iron deficiency anemie (IDA) and/or chronic aplastic anemia (CAA), so as to investigate their relationship.
- Published
- 2002
37. Plasma L-ENK, AVP, ANP and serum gastrin in patients with syndrome of Liver-Qi-stagnation
- Author
-
Guo-Lin Chen, Ze-Qi Chen, Yu-Qiu Zhao, Lin-Jie Shi, and Xue-Wen Li
- Subjects
endocrine system ,medicine.medical_specialty ,business.industry ,Gastroenterology ,Healthy subjects ,Chronic gastritis ,food and beverages ,General Medicine ,Traditional Chinese medicine ,medicine.disease ,Combined Traditional And Modern Medicine ,Pathophysiology ,Serum gastrin ,Endocrinology ,Gastrin levels ,Internal medicine ,medicine ,In patient ,business ,human activities ,hormones, hormone substitutes, and hormone antagonists ,Gastrin - Abstract
AIM:To investigate the pathophysiologic basis of syndrome of Liver-Qi stagnation and parameters for clinical differentiation.METHODS:Plasma L-ENK, AVP, ANP and serum gastrin were determined by RIA in 84 patients with neurasthenia, mastodynia,chronic gastritis, and chronic cholecystitis presenting the same syndrome of Liver-Qi stagnation in traditional Chinese medicine (TCM). Healthy subjects served as controls in comparison with patients having the same syndrome but with different diseases.RESULTS:Among the patients with Liver-Qi stagnation, the plasma L-ENK, ANP and gastrin levels were 38.83ng/L ± 6.32ng/L, 104.11ng/L ± 29.01ng/L and 32.20ng/L ± 6.68ng/L, being significantly lower than those in the healthy controls (P0.01, t = 3.34, 6.17, 4.48). The plasma AVP of the patient group (52.82ng/L ± 19.09ng/L) was significantly higher than that of the healthy controls (P0.01, t = 5.79 =. The above changes in patients having the same symptom complex but different diseases entities showed no significant differences, P0.05.CONCLUSION:The syndrome of Liver-Qi stagnation is closely related to the emotional modulatory abnormality of the brain, with decrease of plasma L-ENK, ANP and gastrin, and increase of plasma AVP as the important pathophysiologic basis.
- Published
- 1999
38. Extensive Alternative Splicing of the Repressor Element Silencing Transcription Factor Linked to Cancer
- Author
-
Gregory M. Miller and Guo-Lin Chen
- Subjects
Epidemiology ,lcsh:Medicine ,Biochemistry ,Gene Splicing ,Exon ,Molecular cell biology ,0302 clinical medicine ,Rapid amplification of cDNA ends ,Neoplasms ,Basic Cancer Research ,Gene expression ,lcsh:Science ,Genetics ,Regulation of gene expression ,0303 health sciences ,Multidisciplinary ,Cancer Risk Factors ,Physics ,Exons ,3. Good health ,Cell biology ,Nucleic acids ,Oncology ,RNA splicing ,Medicine ,Epigenetics ,Research Article ,Genetic Causes of Cancer ,Biophysics ,Biology ,Molecular Genetics ,03 medical and health sciences ,Cancer Genetics ,Humans ,Gene Regulation ,Gene ,030304 developmental biology ,lcsh:R ,Alternative splicing ,Computational Biology ,Exon skipping ,Repressor Proteins ,Biomarker Epidemiology ,Alternative Splicing ,RNA processing ,RNA ,lcsh:Q ,030217 neurology & neurosurgery ,Transcription Factors - Abstract
The repressor element silencing transcription factor (REST) is a coordinate transcriptional and epigenetic regulator which functions as a tumor suppressor or an oncogene depending on cellular context, and a truncated splice variant REST4 has been linked to various types of cancer. We performed a comprehensive analysis of alternative splicing (AS) of REST by rapid amplification of cDNA ends and PCR amplification of cDNAs from various tissues and cell lines with specific primers. We identified 8 novel alternative exons including an alternate last exon which doubles the REST gene boundary, along with numerous 5'/3' splice sites and ends in the constitutive exons. With the combination of various splicing patterns (e.g. exon skipping and alternative usage of the first and last exons) that are predictive of altered REST activity, at least 45 alternatively spliced variants of coding and non-coding mRNA were expressed in a species- and cell-type/tissue-specific manner with individual differences. By examining the repertoire of REST pre-mRNA splicing in 27 patients with kidney, liver and lung cancer, we found that all patients without exception showed differential expression of various REST splice variants between paired tumor and adjacent normal tissues, with striking cell-type/tissue and individual differences. Moreover, we revealed that exon 3 skipping, which causes no frame shift but loss of a domain essential for nuclear translocation, was affected by pioglitazone, a highly selective activator of the peroxisome proliferator-activated receptor gamma (PPARγ) which contributes to cell differentiation and tumorigenesis besides its metabolic actions. Accordingly, this study demonstrates an extensive AS of REST pre-mRNA which redefines REST gene boundary and structure, along with a general but differential link between REST pre-mRNA splicing and various types of cancer. These findings advance our understanding of the complex, context-dependent regulation of REST gene expression and function, and provide potential biomarkers and therapeutic targets for cancer.
- Published
- 2013
39. Alterations of erythrocyte ATPase activity and oxygen consumption in patients with liver-blood deficiency syndrome
- Author
-
Guo-Lin Chen, Lin-Jie Shi, Zi-Qiang Zhang, Jin-Yao Xu, Zhi-Hua Xin, Jun-Fan Liu, Yi-Qin Lu, and Yi-Gang Shu
- Subjects
Adenosine triphosphatase ,medicine.medical_specialty ,Deficiency syndrome ,business.industry ,Gastroenterology ,chemistry.chemical_element ,General Medicine ,medicine.disease ,Traditional Medicine ,Oxygen ,Cell membrane ,Endocrinology ,medicine.anatomical_structure ,Biochemistry ,Iron-deficiency anemia ,chemistry ,Internal medicine ,medicine ,Atpase activity ,In patient ,sense organs ,Aplastic anemia ,business ,skin and connective tissue diseases - Abstract
To investigate the pathophysiology of erythrocyte energy metabolic changes of patients with the traditional Chinese Medicine (TCM) liver-blood deficiency syndrome (LBDS).Erythrocyte membrane ATPase activity and oxygen consumption rate (OCR) were determined in 66 patients with LBDS, including 35 patients with iron deficiency anemia and 31 patients with chronic aplastic anemia. Thirty healthy adults served as controls.ATPase activity and OCR were decreased in patients with LBDS.The decreased erythrocyte ATPase activity and OCR might cause the energy hypometabolism in LBDS patients.
- Published
- 1996
40. Induction of Differentiation by Panaxydol in Human Hepatocarcinoma SMMC-7721 Cells via cAMP and MAP Kinase Dependent Mechanism
- Author
-
WANG, Ze-Jian, primary, SONG, Li, additional, GUO, Lin-Chen, additional, YIN, Min, additional, and SUN, Yong Ning, additional
- Published
- 2011
- Full Text
- View/download PDF
41. On the CpG island methylation status of mitofusin-2 in a vascular smooth muscle cell of phenotype modulation
- Author
-
Yan-hong Luo, Wei Li, Guo-lin Chen, Guangwei Zhong, Zhen-jia Yi, and Lingli Xiang
- Subjects
Cpg island methylation ,Mitofusin-2 ,medicine.anatomical_structure ,Vascular smooth muscle ,business.industry ,Cell ,Medicine ,Cardiology and Cardiovascular Medicine ,business ,Phenotype ,Cell biology - Published
- 2009
42. Human Expression Variation in the Mu-Opioid Receptor is Paralleled in Rhesus Macaque.
- Author
-
Vallender, Eric J., Priddy, Cassandra M., Guo-Lin Chen, and Miller, Gregory M.
- Subjects
GENETIC polymorphisms ,RHESUS monkeys ,PHENOTYPES ,GENETICS ,GENOTYPE-environment interaction ,OPIOID receptors - Abstract
The mu-opioid receptor is a key component in many neurobiological systems including those affecting perceptions of pain and pleasure. In humans and non-human primate model systems, genetic variation in the receptor has been associated with numerous behavioral and physiological traits. In humans, polymorphisms have been identified which affect not only the biochemical function of the receptor, but also expression level. Existing rhesus macaque variation parallels the functional protein changes seen in human, but it remains unknown if expression level differences or concomitant protein changes may also exist. Here we perform a comprehensive survey of naturally occurring polymorphisms in Indian-origin rhesus macaques and identify three 5′ UTR haplotypes with effects on expression level. These expression level effects are in linkage disequilibrium with the previously identified rhesus coding polymorphism C77G. The C77G polymorphism in rhesus parallels the functional effects of the A118G polymorphism in humans and expression level differences occur within both species. Together, the functional variations reported here have implications for future studies seeking to model the opioid system and its associated phenotypes in rhesus macaques. [ABSTRACT FROM AUTHOR]
- Published
- 2008
- Full Text
- View/download PDF
43. Functional characterization of the human TPH2 5′ regulatory region: untranslated region and polymorphisms modulate gene expression in vitro.
- Author
-
Guo-Lin Chen, Vallender, Eric J., and Miller, Gregory M.
- Subjects
- *
GENE expression , *GENETIC polymorphisms , *BEHAVIOR disorders , *PSYCHIATRY , *LUCIFERASES , *ELECTROPHORESIS - Abstract
Tryptophan hydroxylase-2 (TPH2) is a recently identified TPH isoform responsible for neuronal serotonin (5-HT) synthesis, and TPH2 polymorphisms are associated with a range of behavioral traits and psychiatric disorders. This study characterized cis-acting elements and three common polymorphisms (−703G/T, −473T/A, and 90A/G) in the 5′ regulatory region of human TPH2 by using luciferase reporter assay, quantitative real-time PCR, and electrophoretic mobility shift assay (EMSA). The core promoter of human TPH2 was localized to the region between −107 and +7, and the segment of +8 to +53 within the 5′-UTR was found to exert a potent inhibitory effect on gene expression at both transcriptional and post-transcriptional levels. In both RN46A and HEK-293 cell lines, the TTA (−703T/−473T/90A) haplotype of the three polymorphisms showed the lowest gene expression compared with other haplotypes, and the −703G/T and −473T/A polymorphisms tended to exert a synergic effect on gene expression dependent upon the sequence of the 5′-UTR. In RN46A, the 90A/G polymorphism significantly increased luciferase activity and mRNA level irrespective of the other two polymorphisms, while in HEK-293 cells the effect of 90A/G was dependent on the alleles at loci −703 and −473. EMSA showed that all the three polymorphisms potentially alter DNA–protein interactions, while the 90A/G polymorphism predictably alters the 5′-UTR secondary structure of mRNA and influences RNA–protein interactions. In conclusion, our present study demonstrates that both the 5′-UTR and common polymorphisms (especially the 90A/G) in the 5′ regulatory region of human TPH2 have a significant impact on gene expression. [ABSTRACT FROM AUTHOR]
- Published
- 2008
- Full Text
- View/download PDF
44. Balancing selection and the evolution of functional polymorphism in Old World monkey TRIM5α.
- Author
-
Newman, Ruchi M., Hall, Laura, Connole, Michelle, Guo-Lin Chen, Sato, Shuji, Yuste, Eloisa, Diehl, William, Hunters, Eric, Kaur2, Amitinder, Miller, Gregory M., and Johnson, Welkin E.
- Subjects
POLYMORPHISM (Zoology) ,PRIMATES ,HIV ,RETROVIRUSES ,ONCOGENIC viruses ,EVOLUTIONARY theories - Abstract
Retroviral restriction factor TRIM5α exhibits a high degree of sequence variation among primate species. It has been proposed that this diversity is the cumulative result of ancient, lineage-specific episodes of positive selection. Here, we describe the contribution of within-species variation to the evolution of TRIM5α. Sampling within two geographically distinct Old World monkey species revealed extensive polymorphism, including individual polymorphisms that predate speciation (shared polymorphism). In some instances, alleles were more closely related to orthologues of other species than to one another. Both silent and nonsynonymous changes clustered in two domains. Functional assays revealed consequences of polymorphism, including differential restriction of a small panel of retroviruses by very similar alleles. Together, these features indicate that the primate TRIM5α locus has evolved under balancing selection. Except for the MHC there are few, if any, examples of long-term balancing selection in primates. Our results suggest a complex evolutionary scenario, in which fixation of lineage-specific adaptations is superimposed on a subset of critical polymorphisms that predate speciation events and have been maintained by balancing selection for millions of years. [ABSTRACT FROM AUTHOR]
- Published
- 2006
- Full Text
- View/download PDF
45. Endogenous Histamine and Cortisol Levels in Subjects with Different Histamine N-Methyltransferase C314T Genotypes.
- Author
-
Yuen Yi Hon, Jusko, William J., Hong-Hao Zhou, Guo-Lin Chen, Dong Guo, Gan Zhou, Spratlin, Vicky E., and Jann, Michael W.
- Subjects
HISTAMINE ,EPITHELIUM ,GENETIC polymorphisms ,HYDROCORTISONE ,BLOOD plasma ,BLOOD testing ,GENOTYPE-environment interaction - Abstract
Background: Histamine N-methyltransferase (HNMT) catalyzes the methylation of histamine and plays an important role in histamine biotransformation in bronchial epithelium. Enzymatic activity of HNMT has been shown to be regulated by genetic factors, including polymorphisms in the HNMT gene. In this pilot study we determined endogenous levels of histamine and cortisol in plasma and whole blood samples from subjects with different genotypes for the HNMT C314T polymorphism, and investigated whether these parameters differed between individuals with the HNMT CC genotype and those with the CT genotype. Methods: Blood samples were collected from 48 unrelated volunteers (36 males, 12 females), aged 21-40 years, who participated in the study. PCR-restriction fragment length polymorphism analysis was used to determine HNMT C314T genotypes. Erythrocyte HNMT activity was determined as well as plasma and whole blood levels of histamine and cortisol. Two-group comparisons of the various parameters were analyzed by Blocked Wilcoxon test and Wilcoxon Rank Sum test as appropriate. Results: Thirty-seven subjects (24 Caucasians, three African Americans, one Middle Eastern, five Indians, three Chinese, and one Filipino) were found to have the homozygous CC genotype. Ten subjects (eight Caucasians, one Middle Eastern, and one Chinese) were heterozygous and one individual (Pakistani) was homozygous for the variant 314T allele. The frequency of HNMT CT heterozygotes in the small Caucasian cohort was 0.125. Median enzyme activity was significantly lower in subjects with the heterozygous CT genotype than in those with the homozygous CC genotype (485 vs 631 U/mL of red blood cells; p = 0.023). A broad range of histamine levels in plasma and whole blood was observed for all subjects. Whereas the median plasma histamine level was found to be higher in heterozygotes for the wild-type 314C allele than homozygotes (3.32 vs 2.30 nmol/L; p = 0.021), there was no difference between the two groups in histamine levels in whole blood. Cortisol levels were similar between individuals with the homozygous CC genotype and those with the heterozygous CT genotype. Conclusion: Wide variability of plasma and whole-blood histamine levels was observed in subjects with different HNMT C314T genotypes. Endogenous levels of histamine are likely to be affected by various genes and polymorphisms. [ABSTRACT FROM AUTHOR]
- Published
- 2006
- Full Text
- View/download PDF
46. The Influence of St. John's Wort on CYP2C19 Activity with Respect to Genotype.
- Author
-
Lian-Sheng Wang, Bing Zhu, A. M. Abd El-Aty, Gan Zhou, Zhi Li, Jun Wu, Guo-Lin Chen, Jie Liu, Zhi R. Tang, Wang An, Qing Li, Dan Wang, and Hong-Hao Zhou
- Subjects
GENETIC research ,DRUG interactions ,METHYLXANTHINES ,DRUG side effects - Abstract
Induction of cytochrome P450 isozymes is the major cause for clinical drug interactions of St. John'swort. The relationships of St. John'swort to cytochrome P450 isoforms have been fully investigated, but its effect on CYP2C19 is lacking. Thus, the aim ofthe present study was to observe the effect of St. John's wort on CYP2C19 activity using CYP1A2 as a control. Twelve healthy adult men--6 extensive metabolizers of CYP2C19 (2C19*1/2C19*1) and 6 poor metabolizers (42C19*2/2C19*2 and 22C19*2/2C19*3) --were enrolled in a twophase, randomized, crossover manner. All subjects took a 300-mg St. John'swort tablet or placebo three times daily for 14 days, and then the activities of CYP2C19 and CYP1A2 were measured using mephenytoin and caffeine. It was found that St. John's wort treatment significantly increased CYP2C19 activity in CYP2C19 wild-genotype subjects, with urinary 4 -hydroxymephenytoin excretion raised by 151.5% ± 91.9% (p = 0.0156), whereas no significant alteration was observed for CYP2C19 poor metabolizers. Repeated St. John's wort administration did not affect the CYP1A2 phenotypic ratio for both CYP2C19 genotype subjects. In conclusion, St. John's wort is an inducer to the human CYP2C19, and clinicians should pay great attention when St. John's wort is added to or withdrawn from an existing drug regimen containing substrates for such enzymes. [ABSTRACT FROM AUTHOR]
- Published
- 2004
47. Histamine N-methyltransferase gene polymorphisms in Chinese and their relationship with enzyme activity in erythrocytes.
- Author
-
Guo-Lin Chen
- Subjects
- *
GENETIC polymorphisms , *HISTAMINE , *NUCLEOTIDES , *ERYTHROCYTES - Abstract
The aim of this study was to identify polymorphisms in the histamine N-methyltransferase (HNMT) gene in Chinese and to assess their relationship with HNMT activity. One hundred and ninety-two unrelated subjects were recruited. HNMT polymorphisms were screened by direct sequencing with purified polymerase chain reaction products comprising all six exons, plus splice junctions, as well as approximately 2 kb of the 5'-flanking region (5'-FR). Erythrocyte HNMT activity was previously measured by radiochemical microassay. A total of 11 single nucleotide polymorphisms (SNPs) were identified, among which six SNPs had variant allele frequencies greater than 5%. Of the six common SNPs, three (-1637T>C, -463T>C and -411C>T) were located in 5'-FR, one (314C>T) in coding exons, and two (939A>G and 1097A>T) in the 3'-untranslated region (3'-UTR). Most of these common SNPs were in linkage disequilibrium. Genotype-phenotype correlation analyses were performed for those common SNPs in 5'-FR and 3'-UTR. In males, no significant association was found between HNMT activity and these non-coding SNPs. However, in females, the -1637T>C or -463T>C tended to be associated with decreased HNMT activity, whereas the 939A>G or 1097A>T appeared to be correlated with increased enzymatic activity. HNMT polymorphisms differ considerably between Chinese and American. The common SNPs in 5'-FR (-1637T>C and -463T>C) and 3'-UTR (939A>G and 1097A>T) might conditionally regulate the activity of HNMT, or might be genetically linked to unknown mutation(s) underlying the HNMT phenotypic variance. [ABSTRACT FROM AUTHOR]
- Published
- 2003
- Full Text
- View/download PDF
48. Pharmacokinetics of citalopram in relation to genetic polymorphism of CYP2C19.
- Author
-
Bang-Ning, Yu, Guo-Lin, Chen, Nan, He, Dong-Sheng, Ouyang, Xiao-Ping, Chen, Zhao-Qian, Liu, and Hong-Hao, Zhou
- Abstract
The study was designed to define the contribution of cytochrome p450 2C19 (CYP2C19) and cytochrome p450 3A4 (CYP3A4) to citalopram N-demethylation and to evaluate the relationship between the disposition of citalopram and CYP2C19 genotype. A single oral 40-mg dose of citalopram was administered to eight extensive metabolizers and five poor metabolizers recruited from 77 healthy Chinese volunteers whose genotypes and phenotypes were predetermined. The plasma concentrations of citalopram and desmethylcitalopram were determined by high-performance liquid chromatography. It was found that the genotype of CYP2C19 had a significant effect on the N-demethylation of citalopram. Poor metabolizers with m1 mutation had higher area under the plasma concentration versus time curve (AUC0--> infinity ) values than did extensive metabolizers. Terminal elimination half-life (t1/2) values of citalopram in poor metabolizers were significantly higher than the values in extensive metabolizers who were either homozygous or heterozygous with CYP2C19*1. The oral clearance (CLoral) of citalopram in poor metabolizers was significantly lower than that of extensive metabolizers. The AUC0--> infinity and maximum plasma concentration (Cmax) of desmethylcitalopram in poor metabolizers were significantly lower than the values of extensive metabolizers. The results show that CYP3A4 is not the major enzyme in the N-demethylation of citalopram among extensive metabolizers. The polymorphism of CYP2C19 plays an important role in the N- demethylation of citalopram in vivo. The extensive metabolizers and poor metabolizers of CYP2C19 had significant difference in disposition of citalopram in vivo.
- Published
- 2003
49. Gender specific association of CYP2C9*3 with hyperlipidaemia in Chinese.
- Author
-
Chen-Hui Luo, Wang, An, Rong-Hua Zhu, Wei-Xia Zhang, Mo, Wei, Bang-Ning Yu, Guo-Lin Chen, Dong-Sheng Ou-Yang, Xiao-Hong Duan, El-Aty, A. M. Abd, and Hong-Hao Zhou
- Subjects
HYPERLIPIDEMIA ,LIPID metabolism disorders ,DISEASES in women ,PATIENTS - Abstract
Aims To investigate the association of CYP2C9* 3 and * 6 with hyperlipidaemia in Chinese. Methods Four hundred and seventy-six Chinese participated in the study, including 211 uncomplicated hyperlipidaemic patients and 265 healthy controls. PCR-RFLP was used to identify CYP2C9* 3 and * 6. Results CYP2C9* 6 was not detected in this study. The allelic frequency of CYP2C9* 3 was 0.039 (95% CI 0.022, 0.056). A nonsignificant difference existed in CYP2C9* 3 frequencies between males and females ( P = 0.605, OR = 1.194, 95% CI 0.610, 2.336), patients and controls ( P = 0.063, OR = 0.506, 95% CI 0.244, 1.049) in the total population. However, in the female group, CYP2C9* 3 frequency in patients with hyperlipidaemia was significantly lower than that in controls ( P < 0.0001, OR = 0.062, 95% CI 0.008, 0.476). Conclusions The association of CYP2C9* 3 with hyperlipidaemia was specific for females in this Chinese population. [ABSTRACT FROM AUTHOR]
- Published
- 2005
- Full Text
- View/download PDF
50. Association between estrogen receptor α gene (ESR1) PvuII (C/T) and XbaI (A/G) polymorphisms and hip fracture risk: evidence from a meta-analysis.
- Author
-
Li Tang, Guo-Lin Cheng, and Zhong-Hua Xu
- Subjects
Medicine ,Science - Abstract
Background and objectiveGenetic factors are important in the pathogenesis of fractures. Notably, estrogen receptor α (ESR1) has been suggested as a possible candidate gene for hip fractures; however, published studies of ESR1 gene polymorphisms have been hampered by small sample sizes and inconclusive or ambiguous results. The aim of this meta-analysis is to investigate the associations between two novel common ESR1 polymorphisms (intron 1 polymorphisms PvuII-rs2234693: C>T and XbaI-rs9340799: A>G) and hip fracture.MethodsCrude odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the strength of the association.ResultsFive case-control and three cohort studies were assessed, including a total of 1,838 hip fracture cases and 14,972 healthy controls. This meta-analysis revealed that the PvuII T allele is a highly significant risk factor for hip fracture susceptibility, with an effect magnitude similar in male and pre-menopausal and post-menopausal female patients. In stratified analysis based on ethnicity, the PvuII T allele remained significantly correlated with increased risk of hip fracture in Caucasian populations; this correlation, however, was not found in Asian populations. Unlike the PvuII polymorphism, we did not find significant differences in the XbaI (A>G) polymorphism allele or genotype distributions of hip fracture patients and controls. We also found no obvious association between the XbaI polymorphism and hip fracture in any of the racial or gender subgroups.ConclusionOur findings show that the ESR1 PvuII T allele may increase the risk of hip fracture and that the XbaI polymorphism is not associated with hip fracture.
- Published
- 2013
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.