The Genetics of Crohn's Disease

被引：201

作者：

Van Limbergen, Johan ^{[1
]}

Wilson, David C. ^{[1
]}

Satsangi, Jack ^{[2
]}

机构：

[1] Royal Hosp Sick Children, Dept Pediat Gastroenterol & Nutr, Edinburgh EH9 1LF, Midlothian, Scotland

[2] Univ Edinburgh, Mol Med Ctr, Gastrointestinal Unit, Inst Genet & Mol Med, Edinburgh EH9 3JW, Midlothian, Scotland

来源：

ANNUAL REVIEW OF GENOMICS AND HUMAN GENETICS | 2009年 / 10卷

基金：

英国医学研究理事会; 英国惠康基金;

关键词：

Crohn's disease; genetics; genome-wide association study; INFLAMMATORY-BOWEL-DISEASE; GENOME-WIDE ASSOCIATION; INTESTINAL EPITHELIAL-CELLS; ENDOPLASMIC-RETICULUM STRESS; TOLL-LIKE RECEPTOR-4; PORE-FORMING TOXIN; SUSCEPTIBILITY LOCI; CHILDHOOD-ONSET; ULCERATIVE-COLITIS; DENDRITIC CELLS;

D O I：

10.1146/annurev-genom-082908-150013

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

From epidemiological data, based on concordance data in family studies, via linkage analysis to genome-wide association studies, we and others have accumulated robust evidence implicating more than 30 distinct genomic loci involved in the genetic susceptibility to Crohn's disease (CD). These loci encode genes involved in a number of homeostatic rnechanisms: innate pattern recognition receptors (NOD2/Ct1RD 15, TLR4, CARD9), the differentiation of Th17-lymphocytes (IL-23R, JAK2, STAT3, CCR6, ICOSLG), autophagy (ATG16L1, IRGM, LRRK2), maintenance of epithelial barrier integrity (IBD5, DLG5, PTGER4, ITLN1, DMBT1, XBP1), and the orchestration of the secondary immune response (HLA-region, TNFSF15/TL1A, IRF5, PTPN2, PTPN22, NKX2-3, IL-12B, IL-18RAP MST1). While many of these loci also predispose to pediatric CD, an additional number of childhood-onset loci have been identified recently (e.g., TNFRSF6B). Not only has the identification of these loci improved our understanding of the pathophysiology of CD, this knowledge also holds real promise for clinical practice.

引用

页码：89 / 116

页数：28

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