Polymorphisms in <i>KCNQ1</i> Are Associated with Gestational Diabetes in a Korean Population

Abstract

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.

Shared Genomics of Type 2 and Gestational Diabetes Mellitus

“…The C allele of the rs2237892 was associated with GDM in two Korean studies (Kwak et al, 2010;Shin et al, 2010) but not in the Chinese study (Zhou et al, 2009). Instead, rs2237896 and rs2237895 were associated with GDM in a Chinese population (Zhou et al, 2009).…”

“…Three studies recruited women with previous GDM as cases (Lauenborg et al, 2009;Rissanen et al, 2000;Watanabe et al, 2007) and controls were women who have gone through pregnancy without GDM (Lauenborg et al, 2009;Watanabe et al, 2007) or normoglycemic men and women (Rissanen et al, 2000). Two studies recruited older nondiabetic women and men (mean age Ͼ 60) as controls (Cho et al, 2009;Kwak et al, 2010). The various diagnostic criteria for GDM used in these studies are summarized in Table 12.1.…”

“…It is hypothesized that TCF7L2 activates many genes downstream of the Wnt signaling cascade, including proglucagon, which encodes the insulinotropic hormone glucagon-like peptide 1 that plays a critical role in blood glucose homeostasis (Yi et al, 2005). Variants of KCNQ1 gene (rs2237892, rs2237895, rs2237896) increased the risk of GDM in Koreans and Chinese (Kwak et al, 2010;Shin et al, 2010;Zhou et al, 2009), although data on other ethnic groups are not available. Polymorphism rs1799859 of ABCC8 was related to GDM in Chinese (Niu et al, 2005) and Finns (Rissanen et al, 2000); however, the sample size was relatively small in these studies.…”

“…Both rs2237892 and rs2237895 were associated with decreased insulin secretion but not with insulin resistance, indicating KCNQ1 conferring a risk for GDM by altering pancreatic beta cell function (Kwak et al, 2010). Haplotype analysis of rs2237892 and rs2237895 showed that the protective T-A haplotype was signifi cantly associated with decreased risk for GDM (Kwak et al, 2010).…”

“…Three studies have investigated association between KCNQ1 gene and GDM in Koreans (Kwak et al, 2010;Shin et al, 2010) and in Chinese (Zhou et al, 2009). The C allele of the rs2237892 was associated with GDM in two Korean studies (Kwak et al, 2010;Shin et al, 2010) but not in the Chinese study (Zhou et al, 2009).…”