WANG Xueyin, ZHANG Xiaosong, JUAN Juan, GAO Di, TONG Yulong, YANG Huixia.
Chinese Journal of Clinical Obstetrics and Gynecology. 2026, 27(4): 330-334.
Objective To examine the association between polymorphisms of postassium voltage-gated channel subfamily KQT-like member 1 (KCNQ1) gene and the risk of gestational diabetes mellitus (GDM), and their interactions on GDM. Methods This matched case-control study recruited women with GDM and age-matched controls who had a singleton fetus and visited Peking University First Hospital from July 2022 to June 2023. The KCNQ1 rs2237895, rs2237896, rs151290, rs8234 and rs2283228 were genotyped using time-of-flight mass spectrometry genotyping technology. Conditional logistic regression models were conducted to analyze the association between polymorphisms and GDM. Generalized multifactor dimensionality reduction was used to assess interactions between five polymorphisms on GDM. Multivariable linear regression models were used to evaluate the association between polymorphisms and glucose levels. Results This study enrolled 503 women with GDM and 503 age-matched controls. After adjusting for pre-pregnancy body mass index, parity, chronic hypertension and gestational weight gain at 24 weeks’ gestation, KCNQ1 rs2237896 (OR=1.44, 95% CI: 1.06~1.95, P=0.020) and rs2283228 (OR=1.41, 95% CI: 1.04~1.90, P=0.025) were found to be associated with GDM risk in the dominant genetic models, and there was a significant interaction between rs2237896 and rs2283228 on GDM (P=0.011). After multiple adjustment, rs2237896 (β=0.070, 95% CI: 0.010~0.130, P=0.023), rs151290 (β=0.094, 95% CI: 0.032~0.155, P=0.003), rs8234 (β=0.070, 95% CI: 0.001~0.138, P=0.047) and rs2283228 (β=0.076, 95% CI: 0.017~0.134, P=0.012) were associated with fasting glucose in the dominant genetic models, while rs2237896 (β=0.260, 95% CI: 0.007~0.513, P=0.044) and rs2283228 (β=0.347, 95% CI: 0.098~0.596, P=0.006) were related to 1-hour glucose. Conclusions KCNQ1 rs2237896 and rs2283228 were associated with GDM risk, and there was a significant interaction between these two polymorphisms on GDM.