Association between KCNQ1 gene polymorphisms and gestational diabetes mellitus susceptibility in a Chinese population

Yanying Wu^1,2,3Yuxuan Zhang^1,2,3Xin Liu^1,2,3Jia Liu^1,2,3Zhaotao He^1,2,3Yue Wei⁴Qiaoli Zeng^1,2,3*Runmin Guo^1,2,3*

• ¹Department of Internal Medicine, Shunde Women and Children's Hospital (Maternity and Child Healthcare Hospital of Shunde Foshan), Guangdong Medical University, Foshan, China
• ²Key Laboratory of Research in Maternal and Child Medicine and Birth Defects, Guangdong Medical University, Foshan, Guangdong Province, China
• ³Maternal and Child Research Institute, Shunde Women and Children's Hospital (Maternity and Child Healthcare Hospital of Shunde Foshan), Guangdong Medical University., Foshan, China
• ⁴Department of Ultrasound, Shunde Women and Children's Hospital (Maternity and Child Healthcare Hospital of Shunde Foshan), Guangdong Medical University, Foshan, China

The potassium voltage-gated channel subfamily Q member 1 (KCNQ1) gene is recognized as a type 2 diabetes mellitus (T2DM) susceptibility gene. However, there is limited data regarding the association between KCNQ1 gene polymorphisms and gestational diabetes mellitus (GDM) susceptibility in China. To explore the association between KCNQ1 gene polymorphisms and gestational diabetes mellitus (GDM) susceptibility in a Chinese population.We conducted a case-control study including 500 pregnant women with GDM and 502 pregnant women with normal glucose tolerance (as controls). Blood samples and clinical data were collected. KCNQ1 gene rs2237897, rs163184, rs151290, and rs2237892 were genotyped by SNPscan TM genotyping assay. Using SPSS V.26.0, statistical analysis was performed to explore the association of KCNQ1 gene polymorphisms with GDM and genotypes with blood glucose levels. Meta-analysis was further validated in different populations.Results: After being adjusted for confounding factors (age, parity, pre-pregnancy BMI (pre-BMI) and blood pressure) and Bonferroni correction, rs2237897 showed an association with decreased GDM risk in codominant heterozygous (CT vs. CC: OR = 0.537; 95% CI: 0.354-0.816; P = 0.004) and overdominant models (CT vs. CC+TT: OR = 0.533; 95% CI: 0.355-0.801; P = 0.002) in pregnant women aged < 30 years. However, rs2237892, rs151290, and rs163184 did not found associations with GDM after Bonferroni correction. Meta-analysis showed that rs2237892 was associated with decreased GDM risk in different races in dominant (TC+TT vs. CC: OR = 0.830; 95% CI: 0.699-0.985; P = 0.033), recessive (TT vs. CT+CC: OR = 0.733; 95% CI: 0.612-0.877; P = 0.001), codominant homozygous (TT vs. CC: OR = 0.679; 95% CI: 0.562-0.820; P < 0.001), codominant heterozygous (TC vs. CC: OR = 0.843; 95% CI: 0.753-0.945; P = 0.003) and allele models (T vs. C: OR = 0.852; 95% CI: 0.740-0.982; P = 0.027).Conclusion: KCNQ1 rs2237897 is associated with decreased GDM risk in a Chinese population.Although rs2237892 did not found association with GDM risk in our subjects, meta-analysis confirmed that rs2237892 is associated with reduced GDM risk across different populations.Further studies are needed to confirm these findings and elucidate the mechanisms.