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

Journal article

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.

Authors: Banerjee, S; Oneda, B; Yap, L; Jewell, D; Matters, G

• Publication status: Published
• Journal: Mucosal immunology
• Volume: 2
• Issue: 3
• Pages: 220-231
• Publication date: 2009-05-01
• DOI: 10.1038/mi.2009.3
• EISSN: 1935-3456
• ISSN: 1933-0219
• Language: English
• Keywords: Polymorphism, Single Nucleotide; Dextran Sulfate; Humans; Inflammatory Bowel Diseases; Colitis, Ulcerative; Alleles; Mice; Genetic Predisposition to Disease; RNA, Messenger; Animals; Mice, Knockout; Metalloendopeptidases