A novel link between KCNQ1 genetic variants and polycystic ovary syndrome susceptibility

Genome-wide association studies (GWAS) have identified the potassium voltage-gated channel subfamily Q member 1 (KCNQ1) gene, as a potential contributor to the pathogenesis of type 2 diabetes (T2D). Given the known genetic overlap between T2D and polycystic ovary syndrome (PCOS), the present study aimed to investigate the potential association between KCNQ1 gene variants and PCOS susceptibility in a population of Tunisian women. A total of 230 patients and 230 healthy controls were recruited for this case control study. The Rotterdam consensus criteria were used to diagnose patients with PCOS. Genotyping of three KCNQ1 variants (rs231361, rs151290 and rs2237895), was performed using allelic discrimination (real-time PCR). After excluding false positive associations using the false discovery rate adjustment and ensuring statistical power >80%, the present results suggested that the KCNQ1 gene may play a role in PCOS susceptibility. Specifically, the rs231361 variant showed a significant association with an increased risk of PCOS through multiple genetic inheritance models. Additionally, the A/A genotype of the rs231361 variant displayed a correlation with increased levels of triglycerides compared with those with the G/G wild-type and the G/A heterozygous genotypes. To the best of our knowledge, this is the first study to identify the KCNQ1 rs231361 variant as a potential genetic risk factor for PCOS. These findings have important implications for risk assessment and the development of personalized treatment approaches for affected women.