Polymorphisms in the IRS鈥? and PPAR-纬 genes and their association with polycystic ovary syndrome among South Indian women

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• 作者：Shilpi Dasgupta^a ; Pisapati Sirisha^a ; Kudugunti Neelaveni^b ; Katragadda Anuradha^c ; Godi Sudhakar^d ; B. Mohan Reddy^a ; ^{bmr@isical.ac.in} ; ^{bmrisi@gmail.com}
• 关键词：PCOS ; polycystic ovary syndrome ; IRS-1 ; insulin receptor substrate-1 ; PPAR-纬 ; peroxisome proliferator-activated receptor-纬 ; T2DM ; type-2 diabetes mellitus ; TZD ; thiazolidinediones ; INSR ; insulin receptor ; ESHRE ; European Society of Human Reproduction an
• 刊名：Gene
• 出版年：2012
• 期刊代码：73_03781119
• 类别：bio
• 出版时间：15 July, 2012
• 卷：503
• 期：1
• 页码：140-146
• 文件大小：557 K

摘要

Polycystic ovary syndrome is known to be characterized by metabolic abnormalities such as hyperinsulinemia, adiposity and dyslipidemia. Both insulin receptor substrate-1 and peroxisome proliferator-activated receptor-纬 have emerged as significant candidate genes in the pathogenesis of PCOS. In this study, we report for the first time, the association pattern of these genes with PCOS among South Indian women. Two hundred fifty PCOS cases and 299 controls were sequenced for IRS-1 exon1 and PPAR鈥愇?exon 2 and exon 6 to study the already reported SNPs in other ethnic groups and to identify any novel SNP in these exonic regions specific to the Indian population. We did not find any novel SNP in our population except for those already reported- two IRS-1 polymorphisms (Gly972Arg and G2323A) and two PPAR鈥愇?polymorphisms (Pro12Ala and His447His). While the IRS-1 polymorphic alleles had a similar distribution between cases and controls, the PPAR鈥愇?exon 2 Ala allele and exon 6 His447His T allele were significantly more in the controls than in the cases (p 鈮?#xA0;0.05). Haplotype association analysis also suggests that both IRS-1 and PPAR鈥愇?haplotypes with mutations depicted reduced frequency of hyperandrogenic and metabolic traits in PCOS compared to the haplotype with only wild type alleles. Our study on Indian women suggests that while IRS-1, contrary to the earlier findings in other ethnic groups, seems to have a probable protective role against development of specific PCOS sub-phenotypes, the evidence for a probable protective role of PPAR鈥愇?is reaffirmed in our study.