RESUMO
BACKGROUND: PCOS is a common endocrine disorder that is characterized by hyperandrogenism and chronic anovulation and is the leading cause of female infertility. It is a heterogeneous disorder with the involvement of multiple gene and environmental interactions. This study identified variants that are known to confer susceptibility identified by Genome wide association studies (GWAS) in other ethnicities and replicated the same in individuals with PCOS of Indian ethnicity. METHODS: Study subjects (n = 600) were recruited. Blood samples, demographic and clinical details were collected after obtaining informed consent. Fifteen variants were selected from GWA studies from other ethnicities and genotyped in half of the recruited samples (n = 300) using MassARRAYiPLEX™. Replication of significant variants generated from preliminary data was carried out by PCR and direct sequencing in remainder of the samples (n = 300). Insilco analysis for significant variants was performed using software namely CADD, GWAVA, FATHMM-MKL. Relevant statistics were used to ascertain significance. RESULTS: The mean age of patients and controls was 24.26 ± 3.22 and 30.19 ± 11.21 years respectively. Of the 15 variants, 3 variants (rs13405728 in LHCGR; rs13429458 in THADA and rs2209972 IDE genes) were found to be associated with PCOS. The association was successfully replicated in an independent cohort. Insilico analysis categorized two variants (rs13429458-THADA and rs2209972-IDE genes) as deleterious. CONCLUSION: We demonstrate the association of variants in genes namely LHCGR, THADA and IDE with an increased risk of PCOS. Genotyping for these variants aids in identifying at-risk individuals which is crucial as appropriate early interventions may benefit the patient.
