Replication study of THADA rs13429458 variant with PCOS susceptibility and its related traits in Indian women

Abstract

Aim: The aetiopathogenesis of the multigenic multifactorial endocrinopathy, polycystic ovary syndrome (PCOS) has been explored using linkage, candidate gene and genome-wide association studies. Contradictory reports of replication studies attributed to phenotypic, ethnic and geographic variations are available. In this study, we investigated the association of Han Chinese GWAS polymorphism (rs13429458) in thyroid adenoma-associated gene (THADA) with PCOS susceptibility and its related traits in Indian women.

Methods: We genotyped rs13429458 of THADA by direct sequencing and investigated its association with PCOS and its related traits in controls (N = 150) and PCOS women (N = 348). All women were extensively phenotyped in terms of anthropometric, hormonal and metabolic parameters. Association of polymorphism with PCOS risk and its related traits was carried out by regression analysis.

Results: Genotypic and allele frequencies for rs13429458 were not different between controls and PCOS. Women with PCOS carrying variant allele showed significantly reduced fasting glucose levels, and decreased free and bioavailable testosterone and free androgen index.

Conclusion: To our knowledge, this is the first study to demonstrate that although this polymorphism does not alter PCOS susceptibility, it favorably impacts glucose metabolism and hyperandrogenism in Indian women with PCOS only. This study highlights that genetic predisposition markers for PCOS may differ with ethnicity and phenotypic variations.

Keywords: GWAS; Genetics; PCOS; THADA; hyperandrogenism; phenotype.