Premium
The Role of Epistasis in the Etiology of Polycystic Ovary Syndrome among Indian Women: SNP‐SNP and SNP‐Environment Interactions
Author(s) -
Dasgupta Shilpi,
Reddy B. Mohan
Publication year - 2013
Publication title -
annals of human genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.537
H-Index - 77
eISSN - 1469-1809
pISSN - 0003-4800
DOI - 10.1111/ahg.12020
Subject(s) - polycystic ovary , snp , single nucleotide polymorphism , biology , genetics , medicine , multifactor dimensionality reduction , genetic association , candidate gene , endocrinology , oncology , genotype , gene , obesity , insulin resistance
Summary Polycystic Ovary Syndrome (PCOS) is the most common endocrinopathy in women of reproductive age. It is a heterogeneous androgen excess disorder determined by the interaction of multiple genetic and environmental factors. Our earlier analysis on a panel of six candidate genes (Androgen receptor CAG repeats, Follistatin, Luteinizing hormone β subunit, Calpain10, Insulin receptor substrate‐1 and PPARγ ) based on 250 PCOS cases and 299 controls revealed significant association patterns with PCOS among South‐Indian women. We report here for the first time, the SNP‐SNP and SNP‐environment interactions of these genes in the same cohort. Both multivariate logistic regression as well as epistasis analysis (using Multifactor dimensionality reduction software) yielded significant results ( P < 0.05). All CAPN10 SNPs show association (either risk‐conferring or protective) in the obese group, highlighting the importance of this gene in the PCOS pathophysiology. LHP7( LHβ ) and UCSNP44( CAPN10 ) emerged to be the prominent SNPs in the SNP‐SNP interaction analysis. The best SNP‐SNP interaction model was obtained between CAPN10 UCSNP‐44 and PPARγ His447His, implying a significant metabolic component in the PCOS pathology. Replicating our findings in BMI‐specific cohorts in different ethnic populations would be warranted in future to identify the physiological networks in PCOS.