Variants in KCNQ1 are associated with susceptibility to type 2 diabetes mellitus

被引：567

作者：

Yasuda, Kazuki ^{[2
]}

Miyake, Kazuaki ^{[1
]}

Horikawa, Yukio ^{[3
]}

Hara, Kazuo ^{[4
]}

Osawa, Haruhiko ^{[5
]}

Furuta, Hiroto ^{[6
]}

Hirota, Yushi ^{[1
]}

Mori, Hiroyuki ^{[1
]}

Jonsson, Anna ^{[7
]}

Sato, Yoshifumi ^{[8
]}

Yamagata, Kazuya ^{[8
]}

Hinokio, Yoshinori ^{[9
]}

Wang, He-Yao ^{[2
]}

Tanahashi, Toshihito ^{[10
]}

Nakamura, Naoto ^{[11
]}

Oka, Yoshitomo ^{[9
]}

Iwasaki, Naoko ^{[12
]}

Iwamoto, Yasuhiko ^{[12
]}

Yamada, Yuichiro ^{[13
]}

Seino, Yutaka ^{[13
]}

Maegawa, Hiroshi ^{[14
]}

Kashiwagi, Atsunori ^{[14
]}

Takeda, Jun ^{[3
]}

Maeda, Eiichi ^{[15
]}

Shin, Hyoung Doo ^{[16
]}

Cho, Young Min ^{[17
]}

Park, Kyong Soo ^{[17
]}

Lee, Hong Kyu ^{[17
]}

Ng, Maggie C. Y. ^{[18
]}

Ma, Ronald C. W. ^{[18
]}

So, Wing-Yee ^{[18
]}

Chan, Juliana C. N. ^{[18
]}

Lyssenko, Valeriya ^{[7
]}

Tuomi, Tiinamaija ^{[19
,20
]}

Nilsson, Peter ^{[21
]}

Groop, Leif ^{[7
,19
]}

Kamatani, Naoyuki ^{[22
]}

Sekine, Akihiro ^{[23
]}

Nakamura, Yusuke

Yamamoto, Ken ^{[24
]}

Yoshida, Teruhiko ^{[25
]}

Tokunaga, Katsushi ^{[26
]}

Itakura, Mitsuo ^{[10
]}

Makino, Hideichi ^{[5
]}

Nanjo, Kishio ^{[6
]}

Kadowaki, Takashi ^{[4
]}

Kasuga, Masato ^{[1
]}

机构：

[1] Kobe Univ, Grad Sch Med, Dept Internal Med, Div Diabet Metab & Endocrinol, Kobe, Hyogo 6500017, Japan

[2] Int Med Ctr Japan, Res Inst, Dept Metab Disorder, Tokyo 1628655, Japan

[3] Gifu Univ, Sch Med, Dept Endocrinol & Diabet, Div Mol & Struct, Gifu 5011194, Japan

[4] Univ Tokyo, Grad Sch Med, Dept Metab Dis, Tokyo 1138655, Japan

[5] Ehime Univ, Grad Sch Med, Dept Mol & Genet Med, Ehime 7910295, Japan

[6] Wakayama Med Univ, Dept Med 1, Wakayama 6418509, Japan

[7] Lund Univ, Malmo Univ Hosp, Dept Clin Sci Diabet & Endocrinol, S-20502 Malmo, Sweden

[8] Osaka Univ, Grad Sch Med, Dept Metab Med, Osaka 5650871, Japan

[9] Tohoku Univ, Grad Sch Med, Div Mol Metab & Diabet, Sendai, Miyagi 9808574, Japan

[10] Univ Tokushima, Inst Genome Res, Div Genet Informat, Tokushima 7708503, Japan

[11] Kyoto Prefectural Univ Med, Grad Sch Med Sci, Dept Endocrinol & Metab, Kyoto 6028566, Japan

[12] Tokyo Womens Med Univ, Dept Med, Ctr Diabet, Tokyo 1628666, Japan

[13] Kyoto Univ, Sch Med, Dept Diabet & Clin Nutr, Kyoto 6068501, Japan

[14] Shiga Univ Med Sci, Dept Med, Div Endocrinol & Metab, Shiga 5202192, Japan

[15] Kobe Univ, Grad Sch Med, Clin Genome Informat Ctr, Kobe, Hyogo 6500017, Japan

[16] SNP Genet Inc, Dept Genet Epidemiol, Seoul 110834, South Korea

[17] Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul 110744, South Korea

[18] Chinese Univ Hong Kong, Dept Med & Therapeut, Shatin, Hong Kong, Peoples R China

[19] Helsinki Univ Hosp, Dept Med, FIN-00300 Helsinki, Finland

[20] Folkhaelsan Res Ctr, FIN-00014 Helsinki, Finland

[21] Lund Univ, Malmo Univ Hosp, Med Res Unit, Dept Clin Sci, S-20502 Malmo, Sweden

[22] Tokyo Womens Med Univ, Dept Adv Biomed Engn & Sci, Div Gen Med, Tokyo 1628666, Japan

[23] RIKEN, Inst Phys & Chem Res, SNP Res Ctr, Yokohama, Kanagawa 2300045, Japan

[24] Kyushu Univ, Med Inst Bioregulat, Dept Mol Genet, Fukuoka 8128582, Japan

[25] Natl Canc Ctr, Res Inst, Div Genet, Tokyo 1040045, Japan

[26] Univ Tokyo, Grad Sch Med, Dept Human Genet, Tokyo 1130033, Japan

来源：

NATURE GENETICS | 2008年 / 40卷 / 09期

基金：

瑞典研究理事会;

关键词：

D O I：

10.1038/ng.207

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：1092 / 1097

页数：6

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