Replication Study of Candidate Genes Associated With Type 2 Diabetes Based On Genome-Wide Screening

被引：135

作者：

Tabara, Yasuharu ^{[1
]}

Osawa, Haruhiko ^{[2
]}

Kawamoto, Ryuichi ^{[3
]}

Onuma, Hiroshi ^{[2
]}

Shimizu, Ikki ^{[4
]}

Miki, Tetsuro ^{[5
]}

Kohara, Katsuhiko ^{[5
]}

Makino, Hideichi ^{[2
]}

机构：

[1] Ehime Univ, Grad Sch Med, Dept Basic Med Res & Educ, Toon City, Ehime, Japan

[2] Ehime Univ, Grad Sch Med, Dept Mol & Med Genet, Toon City, Ehime, Japan

[3] Seiyo City Nomura Hosp, Dept Internal Med, Seiyo City, Ehime, Japan

[4] Ehime Prefectural Hosp, Dept Internal Med, Toon City, Ehime, Japan

[5] Ehime Univ, Grad Sch Med, Dept Geriatr Med, Toon City, Ehime, Japan

来源：

DIABETES | 2009年 / 58卷 / 02期

关键词：

SUSCEPTIBILITY GENE; RISK LOCI; TCF7L2; VARIANTS; POLYMORPHISMS; RESISTIN; CDKAL1; HHEX;

D O I：

10.2337/db07-1785

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

OBJECTIVE-The present study,vas conducted to confirm possible associations between candidate genes from genome-wide association Studies and type 2 diabetes in Japanese diabetic patients and a community-based general population. A total of 11 previously reported single-nucleotide polymorphisms (SNPs) from the TCF7L2, CDKAL1, HHEX, IGF2BP2, CDKN2A/B, SLC30A8, and KCNJ11 genes were analyzed. RESEARCH DESIGN AND METHODS-Candidate SNPs were genotyped in 506 type 2 diabetic patients and 402 control subjects and meta-analyzed with six previous association studies in Japanese patients. Associations with fasting plasma insulin levels were investigated in a general population sample (n = 1,963, 61 +/- 13 years). RESULTS-In our case-control subjects, susceptibility to type 2 diabetes was replicated in TCF7L2 (rs12255372), CDKAL1 (rs7756992, rs7754840), HHEX (rs7923837), IGF2BP2 (rs4402960 and rs1470579), CDKN2A/B (rs10811661), and SLC30A8 (rs13266634). In addition to these polymorphisms, meta analysis confirmed the association of type 2 diabetes susceptibility with KCNJ11 rs5219, TCF7L2 rs7903146, and HHEX rs111875. The TCF7L2 rs12255372 polymorphism showed the highest odds ratio (OR) for type 2 diabetes (OR 1.714 [1.298-2.263]). Odds ratio of other polymorphisms ranged from 1.13 to 1.41. The risk allele of CDKAL1 rs7756992 was significantly associated with lower insulin levels in type 2 diabetic patients after adjustment for other confounding factors. CONCLUSIONS-Type 2 diabetes susceptibility of seven candidate genes was confirmed in Japanese. Conservation of susceptible loci for type 2 diabetes was independent of ethnic background. Diabetes 58:493-498, 2009

引用

页码：493 / 498

页数：6

共 25 条

[1] Haploview: analysis and visualization of LD and haplotype maps [J].

Barrett, JC ;

Fry, B ;

Maller, J ;

Daly, MJ .

BIOINFORMATICS, 2005, 21 (02) :263-265

[2] Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls [J].

Burton, Paul R. ;

Clayton, David G. ;

Cardon, Lon R. ;

Craddock, Nick ;

Deloukas, Panos ;

Duncanson, Audrey ;

Kwiatkowski, Dominic P. ;

McCarthy, Mark I. ;

Ouwehand, Willem H. ;

Samani, Nilesh J. ;

Todd, John A. ;

Donnelly, Peter ;

Barrett, Jeffrey C. ;

Davison, Dan ;

Easton, Doug ;

Evans, David ;

Leung, Hin-Tak ;

Marchini, Jonathan L. ;

Morris, Andrew P. ;

Spencer, Chris C. A. ;

Tobin, Martin D. ;

Attwood, Antony P. ;

Boorman, James P. ;

Cant, Barbara ;

Everson, Ursula ;

Hussey, Judith M. ;

Jolley, Jennifer D. ;

Knight, Alexandra S. ;

Koch, Kerstin ;

Meech, Elizabeth ;

Nutland, Sarah ;

Prowse, Christopher V. ;

Stevens, Helen E. ;

Taylor, Niall C. ;

Walters, Graham R. ;

Walker, Neil M. ;

Watkins, Nicholas A. ;

Winzer, Thilo ;

Jones, Richard W. ;

McArdle, Wendy L. ;

Ring, Susan M. ;

Strachan, David P. ;

Pembrey, Marcus ;

Breen, Gerome ;

St Clair, David ;

Caesar, Sian ;

Gordon-Smith, Katherine ;

Jones, Lisa ;

Fraser, Christine ;

Green, Elain K. .

NATURE, 2007, 447 (7145) :661-678

[3] TCF7L2 is reproducibly associated with type 2 diabetes in various ethnic groups: a global meta-analysis [J].

Cauchi, Stephane ;

El Achhab, Younes ;

Choquet, Helene ;

Dina, Christian ;

Krempler, Franz ;

Weitgasser, Raimund ;

Nejjari, Chakib ;

Patsch, Wolfgang ;

Chikri, Mohamed ;

Meyre, David ;

Froguel, Philippe .

JOURNAL OF MOLECULAR MEDICINE-JMM, 2007, 85 (07) :777-782

[4] Insulin secretion capacity in the development from normal glucose tolerance to type 2 diabetes [J].

Fukushima, M ;

Suzuki, H ;

Seino, Y .

DIABETES RESEARCH AND CLINICAL PRACTICE, 2004, 66 :S37-S43

[5] Polymorphisms in the IDE-KIF11-HHEX gene locus are reproducibly associated with type 2 diabetes in a Japanese population [J].

Furukawa, Yasushi ;

Shimada, Takeshi ;

Furuta, Hiroto ;

Matsuno, Shohei ;

Kusuyama, Akiko ;

Doi, Asako ;

Nishi, Masahiro ;

Sasaki, Hideyuki ;

Sanke, Tokio ;

Nanjo, Kishio .

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2008, 93 (01) :310-314

[6]

Gavin JR, 1999, DIABETES CARE, V22, pS5

[7] 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

[8] Studies of association of variants near the HHEX, CDKN2A/B, and IGF2BP2 genes with type 2 diabetes and impaired insulin release in 10,705 Danish subjects -: Validation and extension of genome-wide association studies [J].

Grarup, Niels ;

Rose, Chrisian S. ;

Andersson, Ehm A. ;

Andersen, Gitte ;

Nielsen, Arne L. ;

Albrechtsen, Anders ;

Clausen, Jesper O. ;

Rasmussen, Signe S. ;

Jorgensen, Torben ;

Sandbaek, Annelli ;

Lauritzen, Torsten ;

Schmitz, Ole ;

Hansen, Torben ;

Pedersen, Oluf .

DIABETES, 2007, 56 (12) :3105-3111

[9] Association analysis of 6,736 UK subjects provides replication and confirms TCF7L2 as a type 2 diabetes susceptibility gene with a substantial effect on individual risk [J].

Groves, Christopher J. ;

Zeggini, Eleftheria ;

Minton, Jayne ;

Frayling, Timothy M. ;

Weedon, Michael N. ;

Rayner, Nigel W. ;

Hitman, Graham A. ;

Walker, Mark ;

Wiltshire, Steven ;

Hattersley, Andrew T. ;

McCarthy, Mark I. .

DIABETES, 2006, 55 (09) :2640-2644

[10] Replication study for the association of TCF7L2 with susceptibility to type 2 diabetes in a Japanese population [J].

Hayashi, T. ;

Iwamoto, Y. ;

Kaku, K. ;

Hirose, H. ;

Maeda, S. .

DIABETOLOGIA, 2007, 50 (05) :980-984

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