Supplementary Material for: Polymorphisms in <i>KCNQ1</i> Are Associated with Gestational Diabetes in a Korean Population

Background: Recent genome-wide association studies in East Asians have identified polymorphisms in KCNQ1 as new type 2 diabetes risk variants. The aim of this study was to investigate whether variants in KCNQ1 are associated with development of gestational diabetes mellitus (GDM) and measures of oral glucose tolerance test (OGTT) at the time of diagnosis of GDM. Methods: Three candidate single nucleotide polymorphisms (rs2074196, rs2237892, and rs2237895) were genotyped in 869 Korean GDM women and 632 nondiabetic control subjects. Insulin resistance was estimated by homeostasis model assessment and pancreatic β-cell function by the insulinogenic index at 1 h. Results: rs2074196 and rs2237892 were associated with the risk of GDM (OR 1.17, 95% CI 1.01–1.36, p = 0.039; OR 1.24, 95% CI 1.07–1.45, p = 0.0049). Furthermore, rs2237892 and rs2237895 were nominally associated with a decreased insulinogenic index at the time of GDM diagnosis (p = 0.025 and p = 0.037), whereas no association was observed with measures of insulin resistance. Conclusions: The single nucleotide polymorphisms in KCNQ1 showed a significant association with GDM in the Korean population. Although the mechanism is not yet clear, it could be possible that variants in KCNQ1 confer a risk for GDM by altering pancreatic β-cell function.背景：既往针对东亚人群开展的全基因组关联研究(genome-wide association study, GWAS)已将KCNQ1基因多态性确定为2型糖尿病的新型风险变异位点。本研究旨在探讨KCNQ1基因变异是否与妊娠糖尿病(gestational diabetes mellitus, GDM)的发生，以及妊娠糖尿病确诊时的口服葡萄糖耐量试验(oral glucose tolerance test, OGTT)指标相关。 方法：本研究对869名韩国GDM女性受试者及632名非糖尿病对照受试者的3个候选单核苷酸多态性(single nucleotide polymorphism, SNP)位点（rs2074196、rs2237892及rs2237895）进行基因分型。采用稳态模型评估(homeostasis model assessment, HOMA)法评估胰岛素抵抗，以1小时胰岛素生成指数(insulinogenic index, II)评估胰腺β细胞功能。 结果：rs2074196与rs2237892均与GDM发病风险存在显著关联（比值比(odds ratio, OR)=1.17，95%置信区间(confidence interval, CI)=1.01~1.36，P=0.039；OR=1.24，95%CI=1.07~1.45，P=0.0049）。此外，rs2237892与rs2237895在GDM确诊时与胰岛素生成指数降低存在未校正的统计学关联（P=0.025及P=0.037），但未观察到其与胰岛素抵抗指标存在关联。 结论：韩国人群中KCNQ1基因的单核苷酸多态性与GDM存在显著关联。尽管具体发病机制尚未明确，但KCNQ1基因变异可能通过改变胰腺β细胞功能，增加GDM的发病风险。