Association of KCNQ1 Polymorphisms with the Gestational Diabetes Mellitus in Korean Women

Context: Similar genetic factors may play role in the pathogenesis of gestational diabetes mellitus (GDM) and type 2 diabetes mellitus (T2DM). However, genetic studies on GDM are relatively scarce as compared with T2DM. Objective: A recent genome-wide association (GWA) study has proved that three KCNQ1 polymorphisms were significantly associated with the risk of T2DM in various ethnic groups. This study aimed to examine possible genetic effects of these KCNQ1 polymorphisms on the risk of GDM. Design: Three KCNQ1 polymorphisms (rs2074196, rs2237892, and rs2237895) were genotyped using TaqMan assay. The genotype distributions between GDM patients and normal controls were analyzed using logistic regression models. In addition, GDM-related phenotypes were analyzed using multiple regression models. Setting: All GDM patients recruited from Cheil General Hospital in Seoul, Korea, between 2003 and 2008. Participants: Participants included 930 Korean females with GDM and the data of healthy controls from the previous GWA study. Results: KCNQ1 polymorphisms of rs2237892 and rs2237895 were significantly associated with the risk of GDM(P = 0.003 and 0.005, respectively). In the analyses of the GDM-related phenotype, only the risk allele of KCNQ1 rs2237895 was significantly associated with a high-level insulin sensitivity oral glucose tolerance test among patients with GDM(P = 0.0003, 0.004, and 0.05 for codominant, dominant, and recessive models, respectively). Conclusion: KCNQ1 polymorphisms shown to be associated with increased risk for T2DM in the recent GWA study might also represent genetic factors contributing to the development of GDM in Koreans. (J Clin Endocrinol Metab 95: 445-449, 2010)