KCNQ1基因的变异与2型糖尿病易感性相关。
Variants in KCNQ1 are associated with susceptibility to type 2 diabetes mellitus.
作者信息
Yasuda Kazuki, Miyake Kazuaki, Horikawa Yukio, Hara Kazuo, Osawa Haruhiko, Furuta Hiroto, Hirota Yushi, Mori Hiroyuki, Jonsson Anna, Sato Yoshifumi, Yamagata Kazuya, Hinokio Yoshinori, Wang He-Yao, Tanahashi Toshihito, Nakamura Naoto, Oka Yoshitomo, Iwasaki Naoko, Iwamoto Yasuhiko, Yamada Yuichiro, Seino Yutaka, Maegawa Hiroshi, Kashiwagi Atsunori, Takeda Jun, Maeda Eiichi, Shin Hyoung Doo, Cho Young Min, Park Kyong Soo, Lee Hong Kyu, Ng Maggie C Y, Ma Ronald C W, So Wing-Yee, Chan Juliana C N, Lyssenko Valeriya, Tuomi Tiinamaija, Nilsson Peter, Groop Leif, Kamatani Naoyuki, Sekine Akihiro, Nakamura Yusuke, Yamamoto Ken, Yoshida Teruhiko, Tokunaga Katsushi, Itakura Mitsuo, Makino Hideichi, Nanjo Kishio, Kadowaki Takashi, Kasuga Masato
机构信息
Department of Metabolic Disorder, Research Institute, International Medical Center of Japan, Tokyo 162-8655, Japan.
出版信息
Nat Genet. 2008 Sep;40(9):1092-7. doi: 10.1038/ng.207.
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 Pvalue (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.
我们对日本人群进行了2型糖尿病的多阶段全基因组关联研究，共纳入1612例病例、1424例对照以及100000个单核苷酸多态性（SNP）。与KCNQ1基因中的SNP关联最为显著，对该基因进行密集图谱分析发现，第15内含子中的rs2237892显示出最低的P值（6.7×10⁻¹³），优势比（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验证，对总共19930名个体（9569例病例和10361例对照）进行的荟萃分析显示，rs2237892的P值为1.7×10⁻⁴²（OR = 1.40；95%置信区间=1.34 - 1.47）。在对照受试者中，根据β细胞功能的稳态模型评估或校正后的胰岛素反应，该多态性的风险等位基因与胰岛素分泌受损相关。因此，我们的数据表明KCNQ1是不同血统人群中的一个糖尿病易感基因。
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