title: Polymorphisms in the IRS-1 and PPAR-γ genes and their association with polycystic ovary syndrome among South Indian women.
abstract: 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-γ 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-γ 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-γ polymorphisms (Pro12Ala and His447His). While the IRS-1 polymorphic alleles had a similar distribution between cases and controls, the PPAR-γ exon 2 Ala allele and exon 6 His447His T allele were significantly more in the controls than in the cases (p≤0.05). Haplotype association analysis also suggests that both IRS-1 and PPAR-γ 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-γ is reaffirmed in our study.
authors.affiliation: Indian Statistical Institute, Hyderabad, Andhra Pradesh, India.
authors.forename: Shilpi
authors.initials: S
authors.lastname: Dasgupta
authors.forename: Pisapati
authors.initials: P
authors.lastname: Sirisha
authors.forename: Kudugunti
authors.initials: K
authors.lastname: Neelaveni
authors.forename: Katragadda
authors.initials: K
authors.lastname: Anuradha
authors.forename: Godi
authors.initials: G
authors.lastname: Sudhakar
authors.forename: B Mohan
authors.initials: BM
authors.lastname: Reddy
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D015992:Body Mass Index; D005091:Exons; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D017588:Hyperandrogenism / Q000235:genetics; D007194:India / Q000453:epidemiology; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics*; D008875:Middle Aged; D008969:Molecular Sequence Data; D047495:PPAR gamma / Q000235:genetics*; D011085:Polycystic Ovary Syndrome / Q000235:genetics*; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins; D047495:PPAR gamma