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

Abstract

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: S Banerjee, B Oneda, L M Yap, D P Jewell, G L Matters, L R Fitzpatrick, F Seibold, E E Sterchi, T Ahmad, D Lottaz, J S Bond
• Journal: Mucosal immunology (Mucosal Immunol) Vol. 2 Issue 3 Pg. 220-31 (May 2009) ISSN: 1935-3456 [Electronic] United States
• PMID: 19262505 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• RNA, Messenger
• Dextran Sulfate
• Metalloendopeptidases
• meprin A

Topics

• Alleles
• Animals
• Colitis, Ulcerative (genetics, metabolism, pathology)
• Dextran Sulfate
• Genetic Predisposition to Disease
• Humans
• Inflammatory Bowel Diseases (chemically induced, genetics, metabolism, pathology)
• Metalloendopeptidases (genetics, metabolism)
• Mice
• Mice, Knockout
• Polymorphism, Single Nucleotide
• RNA, Messenger (metabolism)