Abstract

REPLICATION OF HIGHLY SIGNIFICANT GWAS AND CANDIDATE GENE SNPS IN THE SOUTHERN INDIAN COHORT OF PCOS WOMEN FROM HYDERABAD

Dr. Kumuda Irgam, Battini Mohan Reddy*, Battini Sriteja Reddy and Sandhya Annamaneni

ABSTRACT

Polycystic ovary syndrome (PCOS) is a heterogeneous disorder with endocrine and metabolic abnormalities in the reproductive aged women. In spite of upsurge in the number of Indian candidate gene studies of PCOS, we have gained very little understanding of the genetic susceptibility profile of the Indian PCOS women. Most of these studies focused on a few SNPs in a small number of samples, and are sporadic in the nature of representation of heterogeneous ethnic and/or regional populations.It is imperative to undertake a large number of studies with adequate sample size and representing the geographic and ethnic heterogeneity of the country to portray the genetic susceptible profile of the Indian PCOS women in general. The present study, together with our recent studies involving a large number of SNPs on the same cohort from Hyderabad, is a significant step forward in this direction. Methods: A panel of 26 SNPs were genotyped, six through RFLP in 250 primary PCOS cases and 299 controls and 20 through SEQUENOM platform in 384 subjects, a random subsets of 192 cases and 192 controls. Results: The allelic association results suggest three SNPs -rs12468394-C (THADA), rs1784692-C (ZBTB16) and rs2234693-C (ESR1) to be significantly associated with PCOS but not after correction for multiple testing. Further, the five loci model was found to be marginally associated with PCOS in gene-gene interaction analysis. Conclusions: It is necessary to test the association of these SNPs in other regions and ethnic groups of India in order to derive the comprehensive genetic susceptible profile of Indian PCOS women.

Keywords: Complex disorder, ethnicity, genetic susceptibility, heterogeneity, metabolic and reproductive abnormalities, single nucleotide polymorphisms.