Association of TCF7L2 Gene Variant (rs12255372) with Polycystic Ovary Syndrome and its Effect Modification of the Disease Phenotype

Polycystic ovary syndrome (PCOS) and type-2 diabetes mellitus (T2DM) share common genetic features. Transcription factor 7-like-2 (TCF7L2 ) is consistently studied T2DM susceptibility locus. However, limited studies on TCF7L2 have failed to demonstrate any link with the PCOS risk. Therefore, we investigated the association of TCF7L2 polymorphic variant (rs12255372) with the PCOS risk. We recruited 120 PCOS cases, diagnosed as per Rotterdam 2003 criteria, and an equal number of age-matched controls. Besides a detailed clinical assessment, subjects underwent biochemical and hormonal profiling. Genotyping for rs12255372 was done by PCR–RFLP. Conditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (95%CIs) of genotype–phenotype correlations. The PCOS cases reported fewer menstrual cycles per year and exhibited signs of hyperandrogenism. The heterozygous genotype of rs12255372 was strongly associated with the PCOS risk (OR = 2.00; 95%CI: 1.07–3.76). Unlike controls, only 3 cases harbored TT genotype, and the PCOS risk persisted in the dominant model (GT + TT) as well. Moreover, we found a synergistic effect modification by the variant genotype in the subjects who had family histories of T2DM, hirsutism, or menstrual irregularities. We report a significant association of the TCF7L2 polymorphic variant rs12255372 with the PCOS risk.