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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.

Original publication

DOI

10.1038/mi.2009.3

Type

Journal article

Journal

Mucosal Immunol

Publication Date

05/2009

Volume

2

Pages

220 - 231

Keywords

Alleles, Animals, Colitis, Ulcerative, Dextran Sulfate, Genetic Predisposition to Disease, Humans, Inflammatory Bowel Diseases, Metalloendopeptidases, Mice, Mice, Knockout, Polymorphism, Single Nucleotide, RNA, Messenger