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