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.
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收藏
页码：220 / 231
页数：12
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