Functional variants of OCTN cation transporter genes are associated with Crohn disease

被引：594

作者：

Peltekova, VD

Wintle, RF

Rubin, LA

Amos, CI

Huang, QQ

Gu, XJ

Newman, B

Van Oene, M

Cescon, D

Greenberg, G

Griffiths, AM

St George-Hyslop, PH

Siminovitch, KA ^{[1
]}

机构：

[1] Univ Toronto, Dept Med, Toronto, ON M5S 1A1, Canada

[2] Univ Toronto, Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Dept Immunol, Toronto, ON M5G 1X5, Canada

[3] Univ Toronto, Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Dept Med Genet & Microbiol, Toronto, ON M5G 1X5, Canada

[4] Toronto Gen Res Inst, Toronto, ON, Canada

[5] Ellipsis Biotherapeut Corp, Toronto, ON M5G 1Z6, Canada

[6] St Michaels Hosp, Div Rheumatol, Toronto, ON M5B 1W8, Canada

[7] Univ Texas, MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA

[8] Hosp Sick Children, Toronto, ON M5G 1X8, Canada

[9] Univ Toronto, Ctr Res Neurodegenerat Dis, Toronto, ON M5S 3H2, Canada

[10] Univ Hlth Network, Toronto, ON, Canada

来源：

NATURE GENETICS | 2004年 / 36卷 / 05期

基金：

美国国家卫生研究院; 加拿大健康研究院;

关键词：

D O I：

10.1038/ng1339

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Crohn disease is a chronic, inflammatory disease of the gastrointestinal tract. A locus of similar to250 kb at 5q31 (IBD5)(1,2) was previously associated with susceptibility to Crohn disease, as indicated by increased prevalence of a risk haplotype of 11 single-nucleotide polymorphisms(3) among individuals with Crohn disease, but the pathogenic lesion in the region has not yet been identified. We report here that two variants in the organic cation transporter cluster at 5q31 ( a missense substitution in SLC22A4 and a G-->C transversion in the SLC22A5 promoter) form a haplotype associated with susceptibility to Crohn disease. These variants alter transcription and transporter functions of the organic cation transporters and interact with variants in another gene associated with Crohn disease, CARD15, to increase risk of Crohn disease. These results suggest that SLC22A4, SLC22A5 and CARD15 act in a common pathogenic pathway to cause Crohn disease.

引用

页码：471 / 475

页数：5

共 27 条

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