Molecular Genetics, Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
PLoS One. 2012;7(3):e32148. doi: 10.1371/journal.pone.0032148. Epub 2012 Mar 5.
Genome-wide association studies in Japanese populations recently identified common variants in the KCNQ1 gene to be associated with type 2 diabetes. We examined the association of these variants within KCNQ1 with type 2 diabetes in a Dutch population, investigated their effects on insulin secretion and metabolic traits and on the risk of developing complications in type 2 diabetes patients.
The KCNQ1 variants rs151290, rs2237892, and rs2237895 were genotyped in a total of 4620 type 2 diabetes patients and 5285 healthy controls from the Netherlands. Data on macrovascular complications, nephropathy and retinopathy were available in a subset of diabetic patients. Association between genotype and insulin secretion/action was assessed in the additional sample of 335 individuals who underwent a hyperglycaemic clamp.
We found that all the genotyped KCNQ1 variants were significantly associated with type 2 diabetes in our Dutch population, and the association of rs151290 was the strongest (OR 1.20, 95% CI 1.07-1.35, p = 0.002). The risk C-allele of rs151290 was nominally associated with reduced first-phase glucose-stimulated insulin secretion, while the non-risk T-allele of rs2237892 was significantly correlated with increased second-phase glucose-stimulated insulin secretion (p = 0.025 and 0.0016, respectively). In addition, the risk C-allele of rs2237892 was associated with higher LDL and total cholesterol levels (p = 0.015 and 0.003, respectively). We found no evidence for an association of KCNQ1 with diabetic complications.
Common variants in the KCNQ1 gene are associated with type 2 diabetes in a Dutch population, which can be explained at least in part by an effect on insulin secretion. Furthermore, our data suggest that KCNQ1 is also associated with lipid metabolism.
最近，日本人群的全基因组关联研究发现 KCNQ1 基因中的常见变异与 2 型糖尿病有关。我们在荷兰人群中研究了 KCNQ1 内这些变体与 2 型糖尿病的关联，研究了它们对胰岛素分泌和代谢特征的影响，以及对 2 型糖尿病患者并发症风险的影响。
在总共 4620 名 2 型糖尿病患者和 5285 名健康对照者中，对 KCNQ1 变体 rs151290、rs2237892 和 rs2237895 进行了基因分型。在糖尿病患者的亚组中，可获得大血管并发症、肾病和视网膜病变的数据。在另外 335 名接受高血糖钳夹术的个体中，评估了基因型与胰岛素分泌/作用之间的关联。
我们发现，在我们的荷兰人群中，所有基因分型的 KCNQ1 变体与 2 型糖尿病显著相关，rs151290 的相关性最强（OR 1.20，95%CI 1.07-1.35，p = 0.002）。rs151290 的风险 C 等位基因与第一相葡萄糖刺激的胰岛素分泌减少有显著关系，而 rs2237892 的非风险 T 等位基因与第二相葡萄糖刺激的胰岛素分泌增加有显著相关性（p = 0.025 和 0.0016，分别）。此外，rs2237892 的风险 C 等位基因与 LDL 和总胆固醇水平升高相关（p = 0.015 和 0.003，分别）。我们没有发现 KCNQ1 与糖尿病并发症之间存在关联的证据。
在荷兰人群中，KCNQ1 基因中的常见变异与 2 型糖尿病相关，这至少可以部分解释为对胰岛素分泌的影响。此外，我们的数据表明，KCNQ1 也与脂质代谢有关。
