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

Mucosal Immunol. 2009 May;2(3):220-31. doi: 10.1038/mi.2009.3. Epub 2009 Mar 4.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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