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Background— Blood pressure (BP) responses to dietary sodium and potassium intervention and cold pressor test vary considerably among individuals. We aimed to identify novel genetic variants influencing individuals’ BP responses to dietary intervention and cold pressor test. Methods and Results— We conducted a genome-wide association study of BP responses in 1881 Han Chinese and de novo genotyped top findings in 698 Han Chinese. Diet-feeding study included a 7-day low-sodium (51.3 mmol/d), a 7-day high-sodium (307.8 mmol/d), and a 7-day high-sodium plus potassium supplementation (60 mmol/d). Nine BP measurements were obtained during baseline observation and each intervention period. The meta-analyses identified 8 novel loci for BP phenotypes, which physically mapped in or near PRMT6 ( P =7.29×10 –9 ), CDCA7 ( P =3.57×10 –8 ), PIBF1 ( P =1.78×10 –9 ), ARL4C ( P =1.86×10 –8 ), IRAK1BP1 ( P =1.44×10 −10 ), SALL1 ( P =7.01×10 –13 ), TRPM8 ( P =2.68×10 –8 ), and FBXL13 ( P =3.74×10 –9 ). There was a strong dose–response relationship between the number of risk alleles of these independent single-nucleotide polymorphisms and the risk of developing hypertension during the 7.5-year follow-up in the study participants. Compared with those in the lowest quartile of risk alleles, odds ratios (95% confidence intervals) for those in the second, third, and fourth quartiles were 1.39 (0.97, 1.99), 1.72 (1.19, 2.47), and 1.84 (1.29, 2.62), respectively ( P =0.0003 for trend). Conclusions— Our study identified 8 novel loci for BP responses to dietary sodium and potassium intervention and cold pressor test. The effect size of these novel loci on BP phenotypes is much larger than those reported by the previously published studies. Furthermore, these variants predict the risk of developing hypertension among individuals with normal BP at baseline.

A straightforward and efficient method to prepare ferrocene-containing allylic amines with excellent regio- and stereoselectivity is reported.

This new method provides a wide range of different substituted total E configured 1,3-dienes starting from simple substrates by using the title multicomponent reaction.

A straightforward and efficient protocol for the highly regio- and stereoselective synthesis of ferrocene-containing allylic amine derivatives via an iodine-mediated iodoamination of ferrocenyl allene was developed. The regio- and stereoselectivity of this reaction may be controlled by the steric effect of the bulky ferrocene group.

The objective of the present study was to review previous investigations on the association of haplotypes in the G-protein β3 subunit (GNB3) gene with representative cardiovascular risk factors/phenotypes: hypertension, overweight, and variation in the systolic and diastolic blood pressures (SBP and DBP, respectively) and as well as body mass index (BMI). A comprehensive literature search was undertaken in Pubmed, Web of Science, EMBASE, Biological Abstracts, LILACS and Google Scholar to identify potentially relevant articles published up to April 2011. Six genetic association studies encompassing 16,068 participants were identified. Individual participant data were obtained for all studies. The three most investigated GNB3 polymorphisms (G-350A, C825T and C1429T) were considered. Expectation–maximization and generalized linear models were employed to estimate haplotypic effects from data with uncertain phase while adjusting for covariates. Study-specific results were combined through a random-effects multivariate meta-analysis. After carefully adjustments for relevant confounding factors, our analysis failed to support a role for GNB3 haplotypes in any of the investigated phenotypes. Sensitivity analyses excluding studies violating Hardy–Weinberg expectations, considering gender-specific effects or more extreme phenotypes (e.g. obesity only) as well as a fixed-effects “pooled” analysis also did not disclose a significant influence of GNB3 haplotypes on cardiovascular phenotypes. We conclude that the previous cumulative evidence does not support the proposal that haplotypes formed by common GNB3 polymorphisms might contribute either to the development of hypertension and obesity, or to the variation in the SBP, DBP and BMI.

Background: Alcohol consumption is heritable, but genetic susceptibility to drinking behavior has not been investigated widely in genome-wide association studies. Objective: We aimed to identify susceptibility loci for drinking behavior (drinkers compared with nondrinkers) in Han Chinese. Design: We performed 2 genome-wide association studies including 1420 drinkers and 3590 nondrinkers in discovery, followed by a de novo replication analysis comprising 4896 drinkers and 13,293 nondrinkers. DNA samples of the subjects were collected for genotyping. Results: The association results of drinking behavior (drinkers or nondrinkers) showed a cluster of single nucleotide polymorphisms at 12q24 in discovery (P , 5 3 10 28 ), with the strongest association for rs11066280 near C12orf51 (P-combined = 3.26 3 10 2215 ). Moreover, we observed the association with drinking behavior for a functional variant in ALDH2 at 12q24 (rs671, P-discovery = 5.17 3 10 235 ). We also identified the association between rs11066280 and daily alcohol intake among drinkers (P-combined = 4.01 3 10 221 ). Conclusion: Our data indicate that common variants at 12q24 may contribute to the susceptibility of drinking behavior in Han Chinese. Am J Clin Nutr doi: 10.3945/ajcn.112.046482.

Many single-nucleotide polymorphisms (SNPs) have been reported to be associated with lipid concentrations in recent genome-wide association studies. The aim of this study was to validate the associations of rs2197089 in the lipoprotein lipase (LPL) gene with serum lipid concentrations and gene expression levels in the Chinese Han population and examine the potential interactions. A total of 9339 participants were recruited and genotyped for rs2197089. Gene expression levels of LPL in blood cells of 309 participants were evaluated by real-time PCR. We observed significant associations between rs2197089 and decreased triglycerides (TG) (P=0.0006), but not high-density lipoprotein cholesterol (HDL-C) concentration (P=0.0881). However, weak evidence of interaction between cigarette smoking and rs2197089 was detected (P=0.0362). In smokers, significant association between rs2197089 and increased HDL-C concentration was found (P=0.0068). Participants with the minor allele A had higher expression levels of LPL (P=0.0243). The results of our study indicated that rs2197089 was significantly associated with TG but it was associated with HDL-C only in smokers. This SNP seemed to have influence on the expression level of LPL.

Over the years, microneedles with varieties of materials and shapes have been fabricated, however, simulation of the penetration of microneedle through the skin are seldom reported. This paper reports on modeling and verification of microneedle-skin interactions. For the first time, a nonlinear hyperelastic model on the micro scale for large deformation is developed to determine several phenomena during the inserting. The accuracy is experimentally verified by measuring the relationship between force and displacements during the insertion of mouse skin. To prove the breakage on the skin, the permeability is tested for diclofenac. The cumulative permeation with pierced skins is 10,000 times larger than untreated counterpart. The simulation results indicated that the maximum insertion force produced when microneedles array was inserted perpendicularly and insertion force increased strongly with the tip width. Based on this model, the design of microneedle can be optimized.

A simple and mild modified method for the first preparation of the title compounds is presented by using an efficient catalyst.

Objective Dozens of single nucleotide polymorphisms (SNPs) in the lipoprotein lipase ( LPL ) gene have been reported to be associated with lipid concentrations. The aim of this study was to validate the association between rs1059611 in the LPL gene and serum lipid concentrations in the Chinese Han population and explore the biological relevance. Methods A total of 5664 participants were recruited and genotyped for the SNP. Gene expression levels of LPL in blood cells were evaluated by real-time PCR and western blotting analysis. The functional potential of the SNP was examined by luciferase reporter assay and electrophoretic mobility-shift assay (EMSA). Results We observed significant associations between rs1059611 and increased HDL-C ( P = 5.65 × 10 −5 ) and decreased TG concentrations ( P = 2.68 × 10 −7 ). We also found that participants with the C allele had higher mRNA expression level ( P = 0.0334) and protein expression level ( P = 0.0641) of LPL . The luciferase activity of the rs1059611 T construct was 0.69-fold of the rs1059611 C construct ( P = 0.0009). The EMSA showed that the binding of the transcription factor(s) differed for the alleles of the SNP. Conclusion The results of our study demonstrated that rs1059611 was associated with HDL-C and TG concentrations in Chinese Han population and might have a functional effect on the transcription of LPL by differential binding of transcription factors.

Genetic factors may determine an individual’s blood pressure (BP) level and risk for hypertension. This study aimed to examine the associations between genetic variants of the adrenomedullin (ADM) gene and essential hypertension, as well as BP levels, in a Chinese Han population. In this study, 2410 hypertensive patients and 2346 normal controls were recruited. Three tagging single-nucleotide polymorphisms (SNPs) based on the HapMap CHB data were selected and genotyped. No significant associations between the three SNPs of the ADM gene and hypertension status were observed. However, SNP rs4399321 was found to be associated with BP levels among the controls. GG homozygotes for this SNP had higher systolic BP (SBP) levels than carriers of the A allele (P=0.002). Particularly in non-drinkers, GG homozygotes had significantly higher SBP (116.9±0.9 vs. 113.7±0.3 mm Hg, P=0.001) and diastolic (74.0±0.7 vs. 72.6±0.2 mm Hg, P=0.046) BP levels than carriers of the A allele. Neither rs4910118 nor rs7944706 was associated with BP levels in the controls either before or after being stratified by drinking status. The results of this study showed that genetic variations in the ADM gene were not associated with the risk of hypertension in a Chinese population. However, the genotype at common variation rs4399321 may influence the BP level in normotensive subjects, especially among non-drinkers. In addition, replications in other populations and further functional studies are required to confirm and interpret the association of ADM with BP.

The Friedel–Crafts acylation of ferrocene catalyzed by a new type of catalyst of rare-earth solid superacid sulfated zirconia SZR3+ was developed. Comparison of catalytic activities between different solid acid catalysts is presented. The catalyst, sulfated zirconia ytterbium SZNYb3+, showed interesting catalytic properties for preparation of acylferrocenes. Furthermore, the catalyst could be regenerated and reused in succession after simple filtration.

BACKGROUND Increased blood pressure (BP) reactivity to cold pressor test (CPT) is a risk factor for hypertension. Genetic factors may influence the variation of BP response to CPT among individuals. We explored the association of genetic variants in the apelin system genes (APLN, APLNR and ACE2) and BP response to CPT in a Chinese population. METHODS A total of 1,998 Han Chinese participants from the Genetic Epidemiology Network of Salt Sensitivity completed a CPT. The percentage changes of BP right after the end of ice-water immersion were used as the measurement of BP responses to CPT. Twenty-two single nucleotide polymorphisms (SNPs) were selected and genotyped, including both tag and potential functional SNPs of the APLN, APLNR, and ACE2 genes. A mixed-effect linear model was used to assess the association between SNPs and BP responses to CPT. RESULTS In women, three SNPs (rs1514283, rs4646176, and rs879922) of the ACE2 gene were significantly associated with the diastolic BP (DBP) response to CPT in the general and recessive genetic models after adjustment for multiple testing (all false discovery rate q < 0.05). There were no significant associations of polymorphisms in APLN and APLNR genes with BP responses to CPT. CONCLUSIONS Our study identified genetic variants in the ACE2 gene that were significantly associated with DBP responses to cold stress in the Chinese female population. Future studies are warranted to confirm these findings.

A new approach for the synthesis of monosubstituted arylferrocenes is based on the coupling of aryldiazonium salts with ferrocene using PEG-1000 as an efficient phase-transfer catalyst.

We performed a meta-analysis of 2 genome-wide association studies of coronary artery disease comprising 1,515 cases with coronary artery disease and 5,019 controls, followed by de novo replication studies in 15,460 cases and 11,472 controls, all of Chinese Han descent. We successfully identified four new loci for coronary artery disease reaching genome-wide significance (P < 5 × 10−8), which mapped in or near TTC32-WDR35, GUCY1A3, C6orf10-BTNL2 and ATP2B1. We also replicated four loci previously identified in European populations (PHACTR1, TCF21, CDKN2A/B and C12orf51). These findings provide new insights into biological pathways for the susceptibility of coronary artery disease in Chinese Han population.

Molybdenum is a promising material for bulk MEMS applications for its high melting point, radiation resistance, high strength and conductivity. This paper reports on the development of wafer level bulk molybdenum ICP etching. Various etching chemistry are explored. The influence of process parameters (coil power/ICP power, platen power/RIE power and gas flow rate) on the etching rate, selectivity to SU-8 mask and etching profile anisotropy are investigated. With an optimized recipe, an etching rate of 2.63μm/min has been achieved with a profile of 70° and samples are employed as electrodes in micro Electrical Discharge Machining (μEDM).

Background Cardiovascular disease (CVD) constitutes a major public health problem in China and worldwide. We aimed to examine classical risk factors and their magnitudes for CVD in a Chinese cohort with over 20 years follow-up. Methods A cohort of 5092 male steelworkers recruited from 1974 to 1980 in Beijing of China was followed up for an average of 20.84 years. Cox proportional-hazards regression model were used to evaluate the risk of developing a first CVD event in the study participants who were free of CVD at the baseline. Results The multivariable-adjusted hazard ratio (HR) associated with every 20 mmHg rise in systolic blood pressure (SBP) was 1.63 in this Chinese male population, which was higher than in Caucasians. Compared to non-smokers, men who smoked not less than one-pack-a-day had a HR of 2.43 (95% confidence interval [CI], 1.75-3.38). The HR (95% CI) for every 20 mg/dl increase in total serum cholesterol (TC) and for every point rise in body mass index (BMI) was 1.13 (1.04-1.23) and 1.06 (1.02-1.09), respectively. Conclusions Our study documents that hypertension, smoking, overweight and hypercholesterolemia are major conventional risk factors of CVD in Chinese male adults. Continued strengthening programs for prevention and intervention on these risk factors are needed to reduce the incidence of CVD in China.

BACKGROUND Recently, fibrillin-1 (FBN1) was reported to play an important role in maintaining the physiological arterial stiffness of essential hypertension (EH). Here, we designed a two-stage case-control study to investigate whether the FBN1 gene harbored any genetic variations associated with EH. METHODS In stage 1, six candidate single-nucleotide polymorphisms (SNPs) of the FBN1 gene were genotyped and tested in 503 cases and 490 controls. SNPs associated with EH (P < 0.05) in stage 1 would be genotyped in stage 2 (814 cases and 779 controls), and analyzed in all the individuals by allele, genotype, haplotype, and diplotype. A meta-analysis was performed and inverse-variance method with random effect model was employed to estimate combined odds ratio (OR) and its 95% confidence interval (CI) for the identified SNPs. RESULTS In stage 1, rs140598 and rs6493333 had statistical association with EH (P < 0.05) and enter stage 2. Multiple logistic regression analysis confirmed that rs140598 but not rs6493333 significantly associated with EH in stage 2 sample. Meta-analysis showed that there was nearly no heterogeneity (I(2) = 0) of genetic variance of rs140598 in the two stages, and the associations of rs140598 in all three genetic models presented statistical significance. Further haplotype analyses showed that the Hap2 (G-C) might decreased the risk of EH when compared with reference haplotype Hap1 (C-C), adjusted OR (95%CI) was 0.823 (0.715-0.948), P = 0.006. CONCLUSION Our finding suggested there is a significant association of rs140598 of FBN1 gene with EH and further replication in other population for association study or prospective study should be warranted.

Background The association between peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PPARGC1A) polymorphisms and type 2 diabetes mellitus (T2DM) has been investigated in several studies, but these studies yielded contradictory results. We conducted a meta-analysis to assess the association between three polymorphisms (Gly482Ser, Thr394Thr and Thr612Met) in PPARGC1A and T2DM. Methods A literature-based search was conducted to collect data. The additive model was chosen to investigate the association between the three polymorphisms and T2DM. The random effects model was used if there was heterogeneity between studies. In addition, subgroup meta-analyses were made according to the ethnic groups. Results Twenty-three studies were enrolled in this meta-analysis (7539 cases and 9562 controls for Gly482Ser, 1818 cases and 2376 controls for Thr394Thr, 2042 cases and 1289 controls for Thr612Met). In the combined analysis of all eligible studies, a significant association was found between Gly482Ser, Thr394Thr and T2DM with pooled odds ratios 1.19 [95% confidence interval (CI) 1.05–1.34] and 1.33 (95% CI 1.04–1.70), respectively, but great heterogeneity was found between studies. In the subgroup meta-analyses, we found that Gly482Ser and Thr394Thr polymorphisms were associated with the risk of T2DM, and the pooled odds ratios were 1.66 (95% CI 1.28–2.15) and 1.72 (95% CI 1.45–2.03), respectively, in the Indian population; no significant evidence was found in the Caucasian and East Asian populations. Conclusions This meta-analysis indicated that Gly482Ser and Thr394Thr polymorphisms of PPARGC1A gene were significantly associated with the risk of T2DM, especially in the Indian population. No relationship was found between the Thr612Met and risk of T2DM. Copyright © 2011 John Wiley & Sons, Ltd.

OBJECTIVES The purpose of this study was to examine the association between genetic variants in the renin-angiotensin system and blood pressure (BP) responses to the cold pressor test (CPT). METHODS The CPT was conducted among 1998 Han Chinese participants. BP measurements were obtained before and after the CPT using a standard sphygmomanometer according to a standard protocol. The association between SNP genotypes and BP responses to the CPT was assessed using a mixed linear model. RESULTS Of 68 SNPs genotyped in six renin-angiotensin system genes, two were strongly associated with DBP responses to CPT (P ≤ 0.001; false discovery rate q value < 0.05): rs2006765 and rs943580 in the angiotensinogen (AGT) gene. Compared to C allele carriers of rs2006765, the TT homozygotes had a significantly decreased DBP response to the CPT. For participants with the TT genotype, percentage DBP responses were 5.68% (4.25-7.10%), compared to corresponding responses of 9.17% (8.66-9.68%) among participants with the CC+CT genotype. In addition, SNP rs4681443 of the angiotensin type 1 receptor (AGTR1) gene was significantly associated with percentage SBP responses to CPT (P ≤ 0.001; q-value

A large proportion of the phenotypic variation in blood pressure (BP) appears to be inherited as a polygenic trait. This study examined the association between 12 single nucleotide polymorphisms (SNPs) in the guanine nucleotide binding protein beta polypeptide 3 (GNB3) and adducin 1 alpha (ADD1) genes and systolic (SBP), diastolic (DBP), and mean arterial (MAP) BP. A total of 3,142 individuals from 636 families were recruited from rural north China, and 2,746 met the eligibility criteria for analysis. BP measurements were obtained using a random-zero sphygmomanometer. Genetic variants were determined using SNPlex assays on an automated DNA Sequencer. A mixed linear model was used to estimate the association between each SNP and BP level. After Bonferroni correction, marker rs4963516 of the GNB3 gene remained significantly associated with DBP (corrected P values = 0.006, 0.007 and 0.002 for co-dominant, additive, and recessive models, respectively) and MAP (corrected P values = 0.02, 0.049, and 0.005, respectively). Compared to carriers of the major A allele, CC homozygotes had higher mean DBP (75.81 +/- 0.62 vs. 73.46 +/- 0.25 mmHg, P = 0.0002) and MAP (91.87 +/- 0.68 vs. 89.42 +/- 0.28 mmHg, P = 0.0004) after adjusting for covariates of age, gender, BMI, study site, and room temperature during BP measurement. In summary, these data support a role for the GNB3 gene in BP regulation in the Chinese population. Future studies aimed at replicating these novel findings are warranted.

Background Elastogenesis of elastic extracellular matrix (ECM) which was recognized as a major component of blood vessels has been believed for a long time to play only a passive role in the dynamic vascular changes of typical hypertension. Emilin1 gene participated in the transcription of ECM's formation and was recognized to modulate links TGF-β maturation to blood pressure homeostasis in animal study. Recently relevant advances urge further researches to investigate the role of Emilin1 gene in regulating TGF-β signals involved in elastogenesis and vascular cell defects of essential hypertension (EH). Methods We designed a two-stage case-control study and selected three single nucleotide polymorphisms (SNPs), rs3754734, rs2011616 and rs2304682 from the HapMap database, which covered Emilin1 gene. Totally 2,586 subjects were recruited from the International Collaborative Study of Cardiovascular Disease in Asia (InterASIA). In stage 1, all the three SNPs of the Emilin1 gene were genotyped and tested within a subsample including 503 cases and 490 controls, significant SNPs would enter into stage 2 including 814 cases with hypertension and 779 controls and analyze on the basis of testing total 2,586 subjects. Results In stage 1, single locus analyses showed that SNPs rs3754734 and rs2011616 had significant association with EH (P < 0.05). In stage 2, weak association for dominant model were observed by age stratification and odds ratio (ORs) of TG+GG vs. TT of rs3754734 were 0.768 (0.584-1.009), 0.985 (0.735-1.320) and 1.346 (1.003-1.806) in < 50, 50-59 and ≥ 60 years group and ORs of GA+AA vs. GG of rs2011616 were 0.745 (0.568-0.977), 1.013 (0.758-1.353) and 1.437 (1.072-1.926) in < 50, 50-59 and ≥ 60 years group respectively. Accordingly, significant interactions were detected between genotypes of rs3754734 and rs2011616 and age for EH, and ORs were 1.758 (1.180-2.620), P = 0.006 and 1.903 (1.281-2.825), P = 0.001, respectively. Results of haplotypes analysis showed that there weren't any haplotypes associated with EH directly, but the interaction of hap2 (GA) and age-group found to be significant after being adjusted for the covariates, OR was 1.220 (1.031-1.444), P value was 0.020. Conclusion Our findings don't support positive association of Emilin1 gene with EH, but the interaction of age and genotype variation of rs3754734 and rs2011616 might increase the risk to hypertension.

Background Atherosclerosis underlies the major pathophysiological mechanisms of coronary heart disease (CHD), and inflammation contributes to all phases of atherosclerosis. C-reactive protein (CRP), a sensitive, but nonspecific marker of inflammation has been shown to play proatherogenic roles in the process of atherosclerosis. Our previous report showed that rs2794521 (-717A>G), located in the promoter of the CRP gene, was independently associated with CHD in Chinese subjects. In the present study, we tried to investigate the biological significance of this genetic variation in vitro. Methods The influence of G to A substitution at the site of rs2794521 on the transcriptional activity of the promoter of the CRP gene was assessed by luciferase reporter assay, and protein binding to the site of rs2794521 was detected by EMSA assay. Results The G to A exchange at the site of rs2794521 resulted in an increased transcriptional activity of the promoter of CRP gene, and glucocorticoid receptor (GR) protein factor bound drastically differently to the A and G alleles at the site of rs2794521. Conclusion These results provided functional evidence supporting the association of the SNP rs2794521 of the CRP gene with CHD probably through regulating the expression level of CRP by different variations of rs2794521.

BACKGROUND Kininogens serve as the precursors of potent vasoactive kinin peptides and also function as cysteine proteinase inhibitors. METHOD Given its potential role in blood pressure homeostasis, a tagging single nucleotide polymorphism (SNP) based case-control study was conducted to explore the association between kininogen 1 gene common variants and essential hypertension in Chinese Han population. Four tagging SNPs were selected on the basis of the HapMap database and further genotyped in 2411 patients with essential hypertension and 2348 controls from the International Collaborative Study of Cardiovascular Disease in Asia (InterASIA in China). RESULTS A significant gender-specific association between the kininogen 1 gene common variants and essential hypertension was observed. In male, but not female participants, rs2304456 CC genotype and rs4686799 TT genotype were significantly related to hypertension [odds ratio (OR) = 2.20, 95% confidence interval (CI): 1.24-3.90, P = 0.007 and OR = 1.31, 95% CI: 1.04-1.66, P = 0.025, respectively]. The haplotypes G-C-C-T and the A-A-T-T were significantly associated with essential hypertension in the male population with adjusted OR 1.43 (P < 0.001) and OR 1.24 (P = 0.001), respectively. The haplotype G-A-C-T was in significant association with essential hypertension (OR = 1.42, P = 0.003) as well as systolic blood pressure (P = 0.005) and diastolic blood pressure (P = 0.015). CONCLUSION This is the first association study of the kininogen 1 gene with essential hypertension. Both single-locus and haplotype analyses indicated the kininogen 1 gene was associated with essential hypertension and blood pressure traits in the Chinese male population.

A concise and efficient protocol for the preparation of cyclopropanes from various aryldiazocarbonyl compounds and electron-deficient olefins catalyzed by Pd(OAc)2 is reported.

The Pd(OAc)2-catalyzed reaction between α-diazocarbonyl compounds and allyl bromides or chlorides leads to the formation of 1,3-diene derivatives.

The Pd(OAc)(2)-catalyzed reaction between alpha-diazocarbonyl compounds and allyl bromides or chlorides leads to the formation of 1,3-diene derivatives.

Background and objective Recent study supports the hypothesis that the abnormalities of vascular smooth muscle cell (VSMC) that alter the intrinsic contractile state of the cell can directly cause abnormal vascular tone and disorders of blood pressure regulation, including hypertension. This study aimed to explore the individual and interactive effects of five genes from the contractile pathway of VSMC (KCNMB1, RGS2, PRKG, ROCK2, and MYLK) on the risk of essential hypertension. Methods Potential functional polymorphisms of the five genes were analyzed in a large, representative Chinese Han sample of 4759 individuals, including 2411 hypertensive patients and 2348 age-matched and sex-matched healthy controls. Results Single locus analyses showed significant association of the alleles of RGS2-rs34717272 with hypertension (original P of Χ 2 test = 0.005; P value of permutation = 0.019). After the adjustment for covariates, the carriers of minor D allele of RGS2-rs34717272 had an increased hypertension risk (DD+ID vs. II; odds ratio = 1.19; 95% confidence interval, 1.04-1.35; P value after the Bonferroni correction = 0.009 x 5 = 0.045). We also found that the carriers of minor T allele of KCNMB1-rs11739136 had a significantly decreased risk for hypertension (TT+CTvs. CC; odds ratio = 0.83; 95% confidence interval, 0.72-0.95; P value after the Bonferroni correction = 0.008 × 5=0.040). Final interaction models were selected and evaluated by permutation test and/or cross-validation test. Both the multifactor-dimensionality reduction and classification and regression trees methods showed a high-order gene-gene interaction among KCNMB1, RGS2, PRKG, and MYLK genes (P value of permutation in multifactor-dimensionality reduction = 0.012). Conclusion The overall results supported that the genetic variants in the contractile pathway of VSMC could contribute to hypertension risk independently or in an interactive manner.

Objective The aim of this study was to investigate the association between common variants in the human tissue kallikrein 1 (KLK1) gene and susceptibility to essential hypertension in Chinese Han. Methods A tagging single nucleotide polymorphism (tSNP) approach was used for a case–control study in 2411 patients with essential hypertension and 2348 controls. All DNA samples and clinical data were collected from the International Collaborative Study of Cardiovascular Disease in Asia (InterASIA). Results Based on the HapMap data of Han Chinese in Beijing (CHB) population, two non-synonymous polymorphisms, namely rs5517 (Glu162Lys) and rs5516 (Gln121Glu), were selected as tSNPs which could efficiently tag eight SNPs of the KLK1 gene with R2 larger than 90% for both haplotypes and single locus. Significant differences were found between groups for frequencies of rs5517 A allele (42.48% in cases versus 39.32% in controls, P = 0.0019) and AA genotype [adjusted odds ratio (OR) = 1.25 for AA versus AG/GG, P = 0.0067]. The haplotype composed of the rs5517 A and rs5516 G allele significantly increased the risk of hypertension, with adjusted OR of 1.12 [95% confidence interval (CI), 1.04–1.28, P = 0.0377] when compared with the common haplotype G–C. Diplotype analysis also showed a significant association between the diplotype of AG–AC and essential hypertension (OR = 1.34, 95% CI, 1.07–1.68, P = 0.0096). Conclusions The present study suggested that rs5517 in the KLK1 gene was significantly associated with essential hypertension in a Chinese Han population.

[3]Ferrocenophane-containing chalcone derivatives with benzene ring (3a–3d) or naphthalene ring (3e–3f) were synthesized and characterized. The potentials for [3]ferrocenophane-containing chalcones cathodically shifted ~70–80 mV compared with those of ferrocene-containing chalcones, indicating easier oxidation by loss of an electron for the former. The thermal behaviours of the prepared compounds were studied by differential scanning calorimetry and polarizing optical microscopy. Compound 3f with terminal alkyl chain of 14 carbon atoms displayed mesophases, whereas other compounds were non-mesomorphic and showed either crystal polymorphic phase transitions or simple melting and freezing process in the heating and cooling cycles.

Summary To investigate the association between polymorphisms in the G protein-coupled receptor kinase 4 gene (GRK4) (R65L, A142V and A486V ) and essential hypertension in northern Han Chinese, we conducted a case-control study consisting of 503 individuals with essential hypertension (HT) and 490 age-, gender-, and area-matched normotensive (NT) controls. The three GRK4 variants were genotyped by PCR-RFLP analysis. Both haplotype and single locus analysis were used to process the genotyping data. The A486 allele showed a significant association with HT (P < 0.001). A total of 6 haplotypes were observed in the entire population, with the haplotypes L-V-A and R-A-A being found to be significantly related to hypertension (P = 0.001).

Essential hypertension is considered to be a typical complex disease with multifactorial etiology, which leads to inconsistent findings in genetic studies. One possibility of failure to replicate some single-locus results is that the underlying genetics of hypertension are not only based on multiple genes with minor effects but also on gene–gene interactions. To test this hypothesis, a case–control study was constructed in Chinese subjects, detecting both single locus and multilocus effects. Eleven candidate genes were selected from biochemical pathways that have been implicated in the development and progression of hypertension, and 33 polymorphisms were evaluated in 503 hypertension patients and 490 age- and gender-matched controls. Single-locus associations, using traditional logistic regression analyses, and multilocus associations, using classification and regression trees and multivariate adaptive regression splines, were both explored in this study. Final models were selected using either Bonferroni correction or cross-validation. Three polymorphisms, TH *rs2070762, ADRB2 *Q27E, and GRK4 *A486V, were found to be independently associated with essential hypertension in Chinese subjects. In addition to these individual predictors, a potential interaction of CYP11B2 - AGTR1 is also involved in the etiology of hypertension. These findings support the multigenic nature of the etiology of essential hypertension and propose a potential gene–gene interactive model for future studies.

To investigate whether variations in the peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) are associated with essential hypertension and type 2 diabetes in a Chinese population. A case-control study design was applied in a Chinese population. Two single nucleotide polymorphisms (SNPs), +1302GA and G482S, in the PGC-1alpha gene were genotyped and compared between 494 unrelated Chinese subjects with essential hypertension and type 2 diabetes and 555 normal control subjects with the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. These two polymorphisms were in highly significant linkage disequilibrium with each other (p0.0001). The frequency of the 482S allele was 42.9% in the Chinese population, which was similar to the frequency in the Japanese population (43.7%), but much higher than those of Caucasian populations (30.8% to 38.1%). There were no associations of the G482S and +1302GA polymorphisms and haplotype combinations with essential hypertension and type 2 diabetes. In addition, no associations were found between these two polymorphisms and blood pressure. In conclusion, these results indicated that these two variations in the PGC-1alpha gene might not contribute to the risk of hypertension and type 2 diabetes in the Chinese population studied here.

The current study investigated the association between PLIN polymorphisms and the combination of hypertension and obesity (HO) and the related clinical features. The polymorphisms 1237 (T/C), 1243 (C/T), and 1323 (C/G) were genotyped in 503 cases with HO and 511 unrelated controls. No associations between polymorphism 1237 (T/C) or 1243 (C/T) and HO were found. However, total cholesterol (TC) levels were significantly different among genotypes of polymorphism 1243 (p = 0.023, power = 0.55). In male cases, 1243T carriers (TT + CT) had higher TC, high-density lipoprotein-cholesterol, and low-density lipoprotein-cholesterol levels compared with CC homozygote carriers (5.23 +/- 0.88 vs. 4.98 +/- 0.90, p = 0.024; 1.13 +/- 0.23 vs. 1.07 +/- 0.22 mM, p = 0.034; 3.3 +/- 0.78 vs. 3.11 +/- 0.80, p = 0.03, respectively). Additionally, 1243T allele carriers were more prevalent among the subjects with both HO and elevated TC levels (> or =5.2 mM) than those with HO and optimal TC levels (

A series of β-ferrocenecarboxyl α-diazocarbonyl compounds were prepared by the reaction of ferrocenoyl chloride with β-hydroxyl α-diazocarbonyl compounds in the presence of pyridine. The diazo decomposition of these ferrocene-containing diazocarbonyl compounds with Rh2(OAc)4 resulted in 2,3-ferrocenecarboxyl migration to give ferrocene-containing α,β-unsaturated esters in high yields.