MEP1A allele for meprin A metalloprotease is a susceptibility gene for inflammatory bowel disease

被引：54

作者：

Banerjee, S. ^{[1
]}

Oneda, B. ^{[2
]}

Yap, L. M. ^{[3
]}

Jewell, D. P. ^{[4
]}

Matters, G. L. ^{[1
]}

Fitzpatrick, L. R. ^{[5
]}

Seibold, F. ^{[6
]}

Sterchi, E. E. ^{[2
]}

Ahmad, T. ^{[7
]}

Lottaz, D. ^{[2
,8
]}

Bond, J. S. ^{[1
]}

机构：

[1] Penn State Univ, Coll Med, Dept Biochem & Mol Biol, Hershey, PA 17033 USA

[2] Univ Bern, Inst Biochem & Mol Med, Bern, Switzerland

[3] Alfred, Dept Gastroenterol, Melbourne, Vic, Australia

[4] Univ Oxford, Radcliffe Infirm, Gastroenterol Unit, Oxford OX2 6HE, England

[5] Penn State Univ, Coll Med, Dept Pharmacol, Hershey, PA USA

[6] Univ Bern, Dept Gastroenterol, Bern, Switzerland

[7] Royal Devon & Exeter Hosp, Dept Gastroenterol, Exeter EX2 5DW, Devon, England

[8] Univ Bern, Inselspital, Dept Rheumatol Clin Immunol & Allergol, CH-3010 Bern, Switzerland

来源：

MUCOSAL IMMUNOLOGY | 2009年 / 2卷 / 03期

基金：

英国惠康基金;

关键词：

DEXTRAN SULFATE SODIUM; INTESTINAL EPITHELIAL-CELLS; GENOME-WIDE ASSOCIATION; INBRED MOUSE STRAINS; ULCERATIVE-COLITIS; CROHNS-DISEASE; BETA-SUBUNITS; METALLOENDOPEPTIDASE MEPRIN; MATRIX METALLOPROTEINASES; DIFFERENTIAL EXPRESSION;

D O I：

10.1038/mi.2009.3

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

The MEP1A gene, located on human chromosome 6p (mouse chromosome 17) in a susceptibility region for inflammatory bowel disease (IBD), encodes the alpha-subunit of metalloproteinase meprin A, which is expressed in the intestinal epithelium. This study shows a genetic association of MEP1A with IBD in a cohort of ulcerative colitis (UC) patients. There were four single-nucleotide polymorphisms in the coding region (P = 0.0012-0.04), and one in the 3 '-untranslated region (P = 2 x 10(-7)) that displayed associations with UC. Moreover, meprin-alpha mRNA was decreased in inflamed mucosa of IBD patients. Meprin-alpha knockout mice exhibited a more severe intestinal injury and inflammation than their wild-type counterparts following oral administration of dextran sulfate sodium. Collectively, the data implicate MEP1A as a UC susceptibility gene and indicate that decreased meprin-alpha expression is associated with intestinal inflammation in IBD patients and in a mouse experimental model of IBD.

引用

页码：220 / 231

页数：12

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