Unoki Hiroyuki, Takahashi Atsushi, Kawaguchi Takahisa, Hara Kazuo, Horikoshi Momoko, Andersen Gitte, Ng Daniel P K, Holmkvist Johan, Borch-Johnsen Knut, Jørgensen Torben, Sandbaek Annelli, Lauritzen Torsten, Hansen Torben, Nurbaya Siti, Tsunoda Tatsuhiko, Kubo Michiaki, Babazono Tetsuya, Hirose Hiroshi, Hayashi Matsuhiko, Iwamoto Yasuhiko, Kashiwagi Atsunori, Kaku Kohei, Kawamori Ryuzo, Tai E Shyong, Pedersen Oluf, Kamatani Naoyuki, Kadowaki Takashi, Kikkawa Ryuichi, Nakamura Yusuke, Maeda Shiro
Laboratory for Endocrinology and Metabolism, Center for Genomic Medicine, RIKEN, Yokohama, Kanagawa 230-0045, Japan.
Nat Genet. 2008 Sep;40(9):1098-102. doi: 10.1038/ng.208.
We conducted a genome-wide association study using 207,097 SNP markers in Japanese individuals with type 2 diabetes and unrelated controls, and identified KCNQ1 (potassium voltage-gated channel, KQT-like subfamily, member 1) to be a strong candidate for conferring susceptibility to type 2 diabetes. We detected consistent association of a SNP in KCNQ1 (rs2283228) with the disease in several independent case-control studies (additive model P = 3.1 x 10(-12); OR = 1.26, 95% CI = 1.18-1.34). Several other SNPs in the same linkage disequilibrium (LD) block were strongly associated with type 2 diabetes (additive model: rs2237895, P = 7.3 x 10(-9); OR = 1.32, 95% CI = 1.20-1.45, rs2237897, P = 6.8 x 10(-13); OR = 1.41, 95% CI = 1.29-1.55). The association of these SNPs with type 2 diabetes was replicated in samples from Singaporean (additive model: rs2237895, P = 8.5 x 10(-3); OR = 1.14, rs2237897, P = 2.4 x 10(-4); OR = 1.22) and Danish populations (additive model: rs2237895, P = 3.7 x 10(-11); OR = 1.24, rs2237897, P = 1.2 x 10(-4); OR = 1.36).
我们在患有2型糖尿病的日本个体及无关对照中，使用207,097个单核苷酸多态性（SNP）标记进行了全基因组关联研究，确定钾离子电压门控通道KQT样亚家族成员1（KCNQ1）是2型糖尿病易感性的一个强有力候选基因。我们在多项独立病例对照研究中检测到KCNQ1中的一个SNP（rs2283228）与该疾病存在一致关联（加性模型P = 3.1×10⁻¹²；比值比[OR]=1.26，95%置信区间[CI]=1.18 - 1.34）。同一连锁不平衡（LD）区域内的其他几个SNP也与2型糖尿病强烈相关（加性模型：rs2237895，P = 7.3×10⁻⁹；OR = 1.32，95% CI = 1.20 - 1.45，rs2237897，P = 6.8×10⁻¹³；OR = 1.41，95% CI = 1.29 - 1.55）。这些SNP与2型糖尿病的关联在新加坡人样本（加性模型：rs2237895，P = 8.5×10⁻³；OR = 1.14，rs2237897，P = 2.4×10⁻⁴；OR = 1.22）和丹麦人群样本（加性模型：rs2237895，P = 3.7×10⁻¹¹；OR = 1.24，rs2237897，P = 1.2×10⁻⁴；OR = 1.36）中得到了重复验证。
