Search

Background: Several long non-coding RNAs are implicated in the development and metastasis of cancer. The non-coding RNA HOTAIR is known to play a significant role in the progression of various cancers. Objectives: This study aimed to assess the impact of HOTAIR dysregulation on stemness markers in AGS and MKN45 gastric cancer cell lines. Methods: Downregulation and upregulation of HOTAIR were induced using small interfering RNA (siRNA) and a HOTAIR overexpression vector, respectively. The surface stemness markers CD24 and CD44 were analyzed using flow cytometry. Additionally, the effects on the expression of two stemness markers, NANOG and P21, were investigated using Quantitative Reverse Transcription PCR (qRT-PCR). Results: Flow cytometry analysis showed that HOTAIR modulates the cell-surface expression of CD44 and CD24 in gastric cancer cells. Furthermore, dysregulation of HOTAIR significantly affected the expression of the genes P21 and NANOG. Conclusions: Our studies suggest that HOTAIR may regulate the stemness characteristics of gastric cancer cell lines. [ABSTRACT FROM AUTHOR]

Background: Hyperphenylalaninemia (HPA) is a metabolic disorder classified into phenylalanine‐4‐hydroxylase (PAH) and non‐PAH deficiency. The latter is produced by mutations in genes involved in the tetrahydrobiopterin (BH4) biosynthesis pathway and DNAJC12 pathogenetic variants. The BH4 metabolism, including de novo biosynthesis involved genes (i.e., guanosine 5′‐triphosphate cyclohydrolase I (GTPCH/GCH1), sepiapterin reductase (SR/SPR), 6‐pyruvoyl‐tetrahydropterin synthase (PTPS/PTS)), and two genes that play roles in cofactor regeneration pathway (i.e., dihydropteridine reductase (DHPR/QDPR) and pterin‐4α‐carbinolamine dehydratase (PCD/PCBD1)). The subsequent systemic hyperphenylalaninemia and monoamine neurotransmitter deficiency lead to neurological consequences. The high rate of consanguineous marriages in Iran substantially increases the incidence of BH4 deficiency. Methods: We utilized the Sanger sequencing technique in this study to investigate 14 Iranian patients with non‐PAH deficiency. All affected subjects in this study had HPA and no mutation was detected in their PAH gene. Results: We successfully identified six mutant alleles in BH4‐deficiency‐associated genes, including three novel mutations: one in QDPR, one in PTS, and one in the PCBD1 gene, thus giving a definite diagnosis to these patients. Conclusion: In this light, appropriate patient management may follow. The clinical effect of reported variants is essential for genetic counseling and prenatal diagnosis in the patients' families and significant for the improvement of precision medicine. [ABSTRACT FROM AUTHOR]

Objectives: This study aims to investigate the association of polymorphism rs10181656 (C>G) of signal transducer and activator of transcription 4 (STAT4) gene with rheumatoid arthritis (RA) and systemic sclerosis (SSc) in the southwest of Iran as well as the probable relationship between the polymorphism with clinical features and disease activity parameters in both diseases. Patients and methods: A total of 200 patients (120 with RA [21 males, 99 females; mean age 44.83 years; range, 16 to 75 years] and 80 with SSc [13 males, 67 females; mean age 44.3 years; range, 30 to 75 years]) and 120 healthy controls (25 males, 95 females; mean age 46.93 years; range, 30 to 75 years) were recruited in this study. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism. A set of genotypes was confirmed by sequencing. Results: A statistically significant association was detected between STAT4 rs10181656 polymorphism and RA (p=0.007). No significant correlation was detected between STAT4 rs10181656 polymorphism and SSc (p=0.357). None of the clinical features (anti-cyclic citrullinated peptide, rheumatoid factor) or disease activity parameters (limited cutaneous SSc, diffuse cutaneous SSc) showed any correlation with the genotype distribution of the STAT4 rs10181656 polymorphism in RA or SSc patients. Conclusion: Our findings suggest an association between RA susceptibility and STAT4 rs10181656 polymorphism. However, no significant association was found between the mentioned polymorphism and SSc. Clinical features and disease activity parameters did not show any association with the polymorphism. [ABSTRACT FROM AUTHOR]

Introduction: Genetic and environmental factors are involved in the incidence of schizophrenia and bipolar disorder. Many reports confirm that several common genes are connected with these two psychotic disorders. Several neurotransmitters may be involved in the molecular mechanisms of schizophrenia and bipolar disorder. We aimed to estimate the role of two talent genes: DAOA in neurotransmission of glutamate and COMT in neurotransmission of dopamine to guide the treatment of schizophrenia and bipolar disorder. Methods: Blood samples (n=100 for schizophrenia, n=100 for bipolar I disorder and n=127 for case control) were collected from individuals unrelated in the southwest of Iran. The SNPs (rs947267 and rs3918342 for DAOA gene/rs165599 and rs4680 for COMT gene) were genotyped using the PCR-RFLP method. Our finding was studied by logistic regression and Mantel-Haenszel Chi-square tests. Results: We observed an association in rs3918342, rs165599 and rs4680 single nucleotide polymorphisms and schizophrenia and bipolar I disorder. In addition, our data demonstrated that the rs947267 was related to bipolar I disorder but there was no association between this SNP and schizophrenia. Conclusion: In conclusion, this result supports the hypothesis that variations in DAOA and COMT genes may play a role in schizophrenia and bipolar disorder. [ABSTRACT FROM AUTHOR]

Copyright of Genetika (0534-0012) is the property of Serbian Genetics Society and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Spinal muscular atrophy (SMA) is the second most common lethal autosomal recessive disease. It is a neuromuscular disorder caused by degenerative of lower motor neurons and occasionally bulbar neurons leading to progressive limb paralysis and muscular atrophy. The SMN1 gene is recognized as a SMA causing gene while NAIP has been characterized as a modifying factor for the clinical severity and age at disease onset in SMA patients (SMA subtypes). The relationship between NAIP deletion and type of SMA remains to be clarified; we investigated this gene alteration in all types of SMA patients. Methods: Molecular analysis was performed on fifty patients with a clinical diagnosis of SMA in Khuzestan province. In addition to common PCR-RFLP analysis for exon 7 and 8 of SMN1 gene, as an internal control we analysed NAIP deletion with PCR of exon 5 of this gene in a multiplex PCR with exon 13 of it. Results: Homozygous-deletion frequency rate for the telomeric copy of SMN (SMN1) exon 7 in all types (type I, II, III) of SMA was approximately 90% and the frequency of deletion in exon 7 and 8 together in all types estimated about 70%. Moreover NAIP gene was deleted in about 60% of these patients and this shows deletion in 91% of type I SMA patients. The correlation between NAIP-deletion and SMN1 mutation showed a high frequency rate. Conclusion: In this study, high frequency of NAIP gene deletion in all type of disease shows the importance role of it in disease pathogenesis. High frequency of NAIP deletion in SMA type I, also shows the importance of the gene in type and severity of disease so it may be a modifier factor in severity of disease. [ABSTRACT FROM AUTHOR]

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the most common hereditary enzymatic disorders in human, increases the vulnerability of erythrocytes to oxidative stress. It is also characterized by remarkable molecular and biochemical heterogeneity. According to previous investigations, G6PD Cosenza (G1376C) is a common G6PD mutation in some parts of Iran. Therefore in the present study we have characterized Cosenza mutation among G6PD deficient individuals in Khuzestan province. In order to identify G6PD Cosenza, we analyzed the G6PD gene in 64 samples out of 231 deficient individuals who had not G6PD Mediterranean mutation, using PCR- restriction fragment length polymorphism (RFLP) method. G6PD Cosenza mutation was found in 6 males of 231 samples, resulting in the relative rate of 2.6% and alíele frequency of 0.023 among Khuzestanian G6PD deficient subjects. A comparison of these results with previous findings in some parts of Iran suggests that G6PD Cosenza is a common mutation in Khuzestanian G6PD deficient individuals. [ABSTRACT FROM AUTHOR]