A novel link between <i>KCNQ1</i> genetic variants and polycystic ovary syndrome susceptibility

Genome-wide association studies (GWAS) have identified the potassium voltage-gated channel subfamily Q member 1 (<i>KCNQ1</i>) 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 <i>KCNQ1</i> 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 <i>KCNQ1</i> 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 <i>KCNQ1</i> 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 <i>KCNQ1</i> 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.