Variants in KCNQ1 are associated with susceptibility to type 2 diabetes mellitus
Variants in KCNQ1 are associated with susceptibility to type 2 diabetes mellitus
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DOI：
10.1038/ng.207
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发表时间：
2008-09-01
期刊：
影响因子：
30.8
通讯作者：
Kasuga, Masato
中科院分区：
文献类型：
--
作者：
Yasuda, Kazuki;Miyake, Kazuaki;Kasuga, Masato
我们对日本2型糖尿病患者进行了一项多阶段全基因组关联研究，共纳入1,612例患者和1,424例对照，并分析了100,000个snp。与KCNQ1的snp相关性最显著，基因内密集定位显示，内含子15中的rs2237892的P值最低(6.7 × 10（-13)，比值比(OR) = 1.49）。KCNQ1与2型糖尿病的关联在韩国、中国和欧洲血统人群以及两个独立的日本人群中得到了重复，对rs2237892进行的荟萃分析共涉及19,930人（9,569例和10,361例对照），P值为1.7 × 10(-42) （OR = 1.40; 95% CI = 1.34-1.47）。在对照组中，根据β细胞功能的稳态模型评估或纠正的胰岛素反应，这种多态性的风险等位基因与胰岛素分泌受损有关。因此，我们的数据暗示KCNQ1是不同祖先群体中的糖尿病易感基因。
We carried out a multistage genome-wide association study of type 2 diabetes mellitus in Japanese individuals, with a total of 1,612 cases and 1,424 controls and 100,000 SNPs. The most significant association was obtained with SNPs in KCNQ1, and dense mapping within the gene revealed that rs2237892 in intron 15 showed the lowest P value (6.7 x 10(-13), odds ratio (OR) = 1.49). The association of KCNQ1 with type 2 diabetes was replicated in populations of Korean, Chinese and European ancestry as well as in two independent Japanese populations, and meta-analysis with a total of 19,930 individuals (9,569 cases and 10,361 controls) yielded a P value of 1.7 x 10(-42) (OR = 1.40; 95% CI = 1.34-1.47) for rs2237892. Among control subjects, the risk allele of this polymorphism was associated with impairment of insulin secretion according to the homeostasis model assessment of beta-cell function or the corrected insulin response. Our data thus implicate KCNQ1 as a diabetes susceptibility gene in groups of different ancestries.