SNPs in KCNQ1 are associated with susceptibility to type 2 diabetes in East Asian and European populations

被引：542

作者：

Unoki, Hiroyuki ^{[1
]}

Takahashi, Atsushi ^{[2
]}

Kawaguchi, Takahisa ^{[3
]}

Hara, Kazuo ^{[4
]}

Horikoshi, Momoko ^{[4
]}

Andersen, Gitte ^{[5
]}

Ng, Daniel P. K. ^{[6
]}

Holmkvist, Johan ^{[5
]}

Borch-Johnsen, Knut ^{[5
,7
,8
]}

Jorgensen, Torben ^{[7
]}

Sandbaek, Annelli ^{[9
]}

Lauritzen, Torsten ^{[9
]}

Hansen, Torben

Nurbaya, Siti ^{[6
]}

Tsunoda, Tatsuhiko ^{[3
]}

Kubo, Michiaki ^{[10
]}

Babazono, Tetsuya ^{[11
]}

Hirose, Hiroshi ^{[12
]}

Hayashi, Matsuhiko ^{[13
]}

Iwamoto, Yasuhiko ^{[11
]}

Kashiwagi, Atsunori ^{[14
]}

Kaku, Kohei ^{[15
]}

Kawamori, Ryuzo ^{[16
]}

Tai, E. Shyong ^{[17
]}

Pedersen, Oluf ^{[5
]}

Kamatani, Naoyuki ^{[2
]}

Kadowaki, Takashi ^{[4
]}

Kikkawa, Ryuichi ^{[14
]}

Nakamura, Yusuke ^{[18
]}

Maeda, Shiro ^{[1
]}

机构：

[1] RIKEN, Lab Endocrinol & Metab, Yokohama, Kanagawa 2300045, Japan

[2] RIKEN, Lab Stat Anal, Yokohama, Kanagawa 2300045, Japan

[3] RIKEN, Lab Med Informat, Ctr Gen Med, Yokohama, Kanagawa 2300045, Japan

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

[5] Steno Diabet Ctr, DK-2820 Copenhagen, Denmark

[6] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Community Occupat & Family Med, Singapore 117597, Singapore

[7] Glostrup Univ Hosp, Res Ctr Prevent & Hlth, DK-2600 Glostrup, Denmark

[8] Univ Aarhus, Fac Hlth Sci, DK-8000 Aarhus, Denmark

[9] Univ Aarhus, Dept Gen Practice, DK-8000 Aarhus, Denmark

[10] RIKEN, Ctr Genom Med, Lab Genotyping Dev, Yokohama, Kanagawa 2300045, Japan

[11] Tokyo Womens Med Univ, Ctr Diabet, Tokyo 1628666, Japan

[12] Keio Univ, Sch Med, Ctr Hlth, Tokyo 1608582, Japan

[13] Keio Univ, Sch Med, Dept Internal Med, Tokyo 1608582, Japan

[14] Shiga Univ Med Sci, Dept Med, Shiga 5202192, Japan

[15] Kawasaki Med Sch, Dept Internal Med, Div Endocrinol & Metab, Okayama 7010192, Japan

[16] Juntendo Univ, Sch Med, Dept Med Metab & Endocrinol, Tokyo 1138421, Japan

[17] Singapore Gen Hosp, Dept Endocrinol, Singapore 169608, Singapore

[18] Univ Tokyo, Inst Med Sci, Ctr Human Genome, Mol Med Lab, Tokyo 1088639, Japan

来源：

NATURE GENETICS | 2008年 / 40卷 / 09期

基金：

英国医学研究理事会;

关键词：

D O I：

10.1038/ng.208

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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).

引用

页码：1098 / 1102

页数：5

共 25 条

[1] Targeted disruption of the Kcnq1 gene produces a mouse model of Jervell and Lange-Nielsen Syndrome [J].

Casimiro, MC ;

Knollmann, BC ;

Ebert, SN ;

Vary, JC ;

Greene, AE ;

Franz, MR ;

Grinberg, A ;

Huang, SP ;

Pfeifer, K .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (05) :2526-2531

[2] A unified stepwise regression procedure for evaluating the relative effects of polymorphisms within a gene using case/control or family data:: Application to HLA in type 1 diabetes [J].

Cordell, HJ ;

Clayton, DG .

AMERICAN JOURNAL OF HUMAN GENETICS, 2002, 70 (01) :124-141

[3]

Cutter J, 2001, B WORLD HEALTH ORGAN, V79, P908

[4] A COMPARISON OF LINKAGE DISEQUILIBRIUM MEASURES FOR FINE-SCALE MAPPING [J].

DEVLIN, B ;

RISCH, N .

GENOMICS, 1995, 29 (02) :311-322

[5] A second generation human haplotype map of over 3.1 million SNPs [J].

Frazer, Kelly A. ;

Ballinger, Dennis G. ;

Cox, David R. ;

Hinds, David A. ;

Stuve, Laura L. ;

Gibbs, Richard A. ;

Belmont, John W. ;

Boudreau, Andrew ;

Hardenbol, Paul ;

Leal, Suzanne M. ;

Pasternak, Shiran ;

Wheeler, David A. ;

Willis, Thomas D. ;

Yu, Fuli ;

Yang, Huanming ;

Zeng, Changqing ;

Gao, Yang ;

Hu, Haoran ;

Hu, Weitao ;

Li, Chaohua ;

Lin, Wei ;

Liu, Siqi ;

Pan, Hao ;

Tang, Xiaoli ;

Wang, Jian ;

Wang, Wei ;

Yu, Jun ;

Zhang, Bo ;

Zhang, Qingrun ;

Zhao, Hongbin ;

Zhao, Hui ;

Zhou, Jun ;

Gabriel, Stacey B. ;

Barry, Rachel ;

Blumenstiel, Brendan ;

Camargo, Amy ;

Defelice, Matthew ;

Faggart, Maura ;

Goyette, Mary ;

Gupta, Supriya ;

Moore, Jamie ;

Nguyen, Huy ;

Onofrio, Robert C. ;

Parkin, Melissa ;

Roy, Jessica ;

Stahl, Erich ;

Winchester, Ellen ;

Ziaugra, Liuda ;

Altshuler, David ;

Shen, Yan .

NATURE, 2007, 449 (7164) :851-U3

[6] Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes [J].

Grant, SFA ;

Thorleifsson, G ;

Reynisdottir, I ;

Benediktsson, R ;

Manolescu, A ;

Sainz, J ;

Helgason, A ;

Stefansson, H ;

Emilsson, V ;

Helgadottir, A ;

Styrkarsdottir, U ;

Magnusson, KP ;

Walters, GB ;

Palsdottir, E ;

Jonsdottir, T ;

Gudmundsdottir, T ;

Gylfason, A ;

Saemundsdottir, J ;

Wilensky, RL ;

Reilly, MP ;

Rader, DJ ;

Bagger, Y ;

Christiansen, C ;

Gudnason, V ;

Sigurdsson, G ;

Thorsteinsdottir, U ;

Gulcher, JR ;

Kong, A ;

Stefansson, K .

NATURE GENETICS, 2006, 38 (03) :320-323

[7] Gene-based SNP discovery as part of the Japanese Millennium Genome Project: identification of 190562 genetic variations in the human genome [J].

Haga, H ;

Yamada, R ;

Ohnishi, Y ;

Nakamura, Y ;

Tanaka, T .

JOURNAL OF HUMAN GENETICS, 2002, 47 (11) :605-610

[8]

Jorgensen Torben, 2003, Eur J Cardiovasc Prev Rehabil, V10, P377

[9] The ADDITION study: proposed trial of the cost-effectiveness of an intensive multifactorial intervention on morbidity and mortality among people with Type 2 diabetes detected by screening [J].

Lauritzen, T ;

Griffin, S ;

Borch-Johnsen, K ;

Wareham, NJ ;

Wolffenbuttel, BHR ;

Rutten, G .

INTERNATIONAL JOURNAL OF OBESITY, 2000, 24 (Suppl 3) :S6-S11

[10] Targeted disruption of the Kvlqt1 gene causes deafness and gastric hyperplasia in mice [J].

Lee, MP ;

Ravenel, JD ;

Hu, RJ ;

Lustig, LR ;

Tomaselli, G ;

Berger, RD ;

Brandenburg, SA ;

Litzi, TJ ;

Bunton, TE ;

Limb, C ;

Francis, H ;

Gorelikow, M ;

Gu, H ;

Washington, K ;

Argani, P ;

Goldenring, JR ;

Coffey, RJ ;

Feinberg, AP .

JOURNAL OF CLINICAL INVESTIGATION, 2000, 106 (12) :1447-1455

← 1 2 3 →