The G2964A 3'-untranslated region polymorphism of the signal transducer and activator of transcription 6 gene is associated with endometriosis in South Indian women

Background: The aim of the study was to test whether the signal transducer and activator of transcription 6 (STAT6) gene influences the risk of developing endometriosis. Methods: The single-nucleotide polymorphism, G2964A, in the 3'-untranslated region (UTR) of the STAT6 gene was tested for association in a case-control study of 232 affected women and 210 women with no evidence of disease. All the women were infertile, ascertained from the same infertility clinic and of South Indian origin. The genotype frequencies of this polymorphism were compared using PCR and sequencing analysis. Results: There were statistically significant differences in the genotype distributions (P = 0.002) and allele frequencies (P = 0.0002) between the cases and controls, according to codominant, dominant and recessive genotype models. Conclusions: We report for the first time an association between the STAT6 G2964A 3'-UTR polymorphism and endometriosis in South Indian women. This finding suggests that STAT6 may contribute to disease susceptibility in endometriosis, which carries an extra interest as the gene lies in a region which has been implicated, albeit weakly, in a previous genomewide scan

The interleukin-6 −174G/C promoter polymorphism is not associated with endometriosis in South Indian women

Objective: To investigate the association of the −174 G/C promoter polymorphism of the interleukin-6 (IL-6) gene with endometriosis in South Indian women. Methods: The genotype frequencies of the common IL-6174 G/C polymorphism were compared in infertility patients with (n = 232) and without (n = 210) endometriosis using polymerase chain reaction (PCR) and sequencing analysis. Results: The genotype frequencies among the cases and controls were G/G 62.9% and 71.9%, G/C 34. 1% and 25.2%, and C/C 3.0% and 2.9%. The G and C allele frequencies were 80% and 84.6%, and 20% and 15.4%, respectively. There were no statistically signficant differences in the genotype distributions or allele frequencies between the cases and controls (P = .12). Conclusions: The present study demonstrates no signficant association between the IL-6 -174 G/C promoter polymorphism and endometriosis in South Indian women

Histone deacetylase 1, Sirtuin 1, and Sirtuin 3 single-nucleotide polymorphisms and the risk of endometriosis in South Indian women

The aim of the study was to investigate the association between Histone deacetylase 1 (HDAC1), Sirtuin1 (SIRT1), and Sirtuin3 (SIRT3) single-nucleotide polymorphisms (SNPs) and risk of endometriosis in South Indian women. A total of 300 subjects were recruited in this case-control study comprising 150 affected women and 150 women with no evidence of disease. All the subjects were of South Indian origin. The genotyping of HDAC1, SIRT1, and SIRT3 SNPs (rs1741981T/C, rs144124002A/G, and rs536715G/A) was carried out on DNA from subjects by PCR-RFLP and sequencing analysis. The genotype (p = .00782) and allele (p = .02561) frequencies of the HDAC1 rs1741981 polymorphism showed significant difference between cases and controls. In contrast, SIRT1 (rs144124002) and SIRT3 (rs536715) SNPs did not show significant association with the disease. The HDAC1 polymorphism may constitute a heritable risk factor for endometriosis in South Indian women. To date, there is no reported study on the association of polymorphisms in HDAC1, SIRT1, and SIRT3 with endometriosis risk. Impact Statement What is already known on this subject? Endometriosis is a benign gynaecological disease characterised by the implantation of functional endometrial tissue at ectopic positions, associated with an increased risk of malignant transformation. Epigenetic mechanisms are essential for normal development and maintenance of tissue-specific gene expression patterns. Histone modification, including deacetylation of lysine residues by HDACs, is a key epigenetic mechanism of gene expression regulation in endometriosis, therefore genetic variation in HDACs causing epigenetic control defects might lead to disease susceptibility. What do the results of this study add? Our study shows that the HDAC1 SNP is significantly associated with endometriosis in South Indian women, whereas the SNPs of SIRT1 and SIRT3 could not show any association with the disease. What are the implications of these findings for clinical practice and/or further research? The polymorphism of HDAC1 rs1741981 could be used as an important marker of genetic susceptibility to endometriosis development. Analysis of this SNP might help to identify patients at high risk for disease outcome

The endothelial nitric oxide synthase Glu298Asp polymorphism is not a risk factor for endometriosis in South Indian women

Objective: To investigate whether the eNOS gene influences the risk of developing endometriosis in south Indian women. Study design: The single nucleotide polymorphism, Glu298Asp, in exon7 of the eNOS gene was tested for association in a case-control study of 232 affected women and 210 women with no evidence of disease. All the women were infertile, ascertained from the same infertility clinic. The genotype frequencies of the polymorphism were compared, using polymerase chain reaction and sequencing analysis. The localization and expression of eNOS in the eutopic endometrium of five cases and four controls was also analyzed using immunohistochemistry and western blotting. Results: No statistically significant differences were observed in the genotype distributions and allele frequencies (p = 0.3) between the cases and controls according to codominant, dominant and recessive genotype models. The localization and expression of this protein were similar in the endometrium of cases and controls. Conclusion: In the present study we could neither observe a difference in the eNOS expression nor establish an association between the eNOS Glu298Asp exon 7 polymorphism in south Indian women with endometriosis

Therapeutic effect of green tea extract on alcohol induced hepatic mitochondrial DNA damage in albino wistar rats

The present study principally sought to investigate the effect of green tea extract (GTE) supplementation on hepatic mitochondrial DNA (mtDNA) damage in alcohol receiving rats. MtDNA was isolated from hepatic tissues of albino wistar rats after alcohol treatment with and without GTE supplementation. Entire displacement loop (D-loop) of mtDNA was screened by PCR-Sanger’s sequencing method. In addition, mtDNA deletions and antioxidant activity were measured in hepatic tissue of all rats. Results showed increased frequency of D-loop mutations in alcoholic rats (ALC). DNA mfold analysis predicted higher free energy for 15507C and 16116C alleles compared to their corresponding wild alleles which represents less stable secondary structures with negative impact on overall mtDNA function. Interestingly, D-loop mutations observed in ALC rats were successfully restored on GTE supplementation. MtDNA deletions were observed in ALC rats, but intact native mtDNA was found in ALC + GTE group suggesting alcohol induced oxidative damage of mtDNA and ameliorative effect of GTE. Furthermore, markedly decreased activities of glutathione peroxidise, superoxide dismutase, catalase and glutathione content were identified in ALC rats; however, GTE supplementation significantly (P < 0.05) restored these levels close to normal. In conclusion, green tea could be used as an effective nutraceutical against alcohol induced mitochondrial DNA damage

Vitamin D receptor gene polymorphisms and risk of polycystic ovary syndrome in South Indian women

<p>Polycystic ovary syndrome (PCOS) is the most common endocrine disorder of reproductive age women. Emerging evidence suggests that Vitamin D Receptor (VDR) might be a causal factor for characteristics associated with PCOS such as obesity and type 2 diabetes. Present study investigated association between VDR gene BsmI A/G (rs1544410), ApaI A/C (rs7975232) and TaqI T/C (rs731236) single nucleotide polymorphisms and PCOS risk in South Indian women. Genotyping of VDR gene SNPs was carried out in PCOS patients (<i>n</i> = 95) and controls (<i>n</i> = 130) by PCR-RFLP method and confirmed by sequencing analysis. Haplotype frequencies for multiple loci and the standardized disequilibrium coefficient (D′) for pairwise linkage disequilibrium (LD) were assessed by Haploview software. Results showed significantly increased frequencies of BsmI G/G (<i>p</i> = .0197), ApaI C/C (<i>p</i> = .048), TaqI C/C (<i>p</i> = .044) genotypes and BsmI G (<i>p</i> = .0181), ApaI C (<i>p</i> = .0092), TaqI C (<i>p</i> = .0066) alleles in patients compared to controls. In addition, the frequency of the ‘BsmI G, ApaI C, TaqI C’ haplotype was also significantly elevated in patients (<i>p</i> = .0087). In conclusion, the VDR gene BsmI A/G ApaI A/C TaqI T/C and haplotype may constitute an inheritable risk factor for PCOS in South Indian women.</p

Mitochondrial Genome Variations in Advanced Stage Endometriosis: A Study in South Indian Population

<div><h3>Background</h3><p>Endometriosis is a chronic gynecological benign disease that shares several features similar to malignancy. Mitochondrial DNA (mtDNA) mutations have been reported in all most all types of tumors. However, it is not known as to whether mtDNA mutations are associated with endometriosis.</p> <h3>Methodology</h3><p>We sequenced the entire mitochondrial genome of analogous ectopic and eutopic endometrial tissues along with blood samples from 32 advanced stage endometriosis patients to analyze the role of somatic and germ-line mtDNA variations in pathogenesis of endometriosis. All ectopic tissues were screened for tumor-specific mtDNA deletions and microsatellite instability (MSI). We also performed mtDNA haplogrouping in 128 patients and 90 controls to identify its possible association with endometriosis risk.</p> <h3>Principal Findings</h3><p>We identified 51 somatic (novel: 31; reported: 20) and 583 germ-line mtDNA variations (novel: 53; reported: 530) in endometriosis patients. The A13603G, a novel missense mutation which leads to a substitution from serine to glycine at the codon 423 of ND5 gene showed 100% incidence in ectopic tissues. Interestingly, eutopic endometrium and peripheral leukocytes of all the patients showed heteroplasmy (A/G; 40–80%) at this locus, while their ectopic endometrium showed homoplasmic mutant allele (G/G). Superimposition of native and mutant structures of ND5 generated by homology modeling revealed no structural differences. Tumor-specific deletions and MSI were not observed in any of the ectopic tissues. Haplogrouping analysis showed a significant association between haplogroup M5 and endometriosis risk (<em>P</em>: 0.00069) after bonferroni correction.</p> <h3>Conclusions</h3><p>Our findings substantiate the rationale for exploring the mitochondrial genome as a biomarker for the diagnosis of endometriosis.</p> </div