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

S Banerjee1, B Oneda, L M Yap

  • 1Department of Biochemistry & Molecular Biology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA.

Mucosal Immunology
|March 6, 2009
PubMed

Insights

The MEP1A gene is linked to ulcerative colitis (UC), a type of inflammatory bowel disease (IBD). Reduced meprin-alpha expression in the gut is associated with IBD severity in patients and mouse models.

Area of Science:

  • Genetics
  • Gastroenterology
  • Immunology

Background:

  • The MEP1A gene, encoding meprin-alpha, is located in a region associated with inflammatory bowel disease (IBD).
  • Meprin-alpha is expressed in the intestinal epithelium, suggesting a role in gut health.

Purpose of the Study:

  • To investigate the association of the MEP1A gene with ulcerative colitis (UC), a major form of IBD.
  • To examine the role of meprin-alpha expression in intestinal inflammation.

Main Methods:

  • Genetic association study of single-nucleotide polymorphisms (SNPs) in the MEP1A gene in a cohort of UC patients.
  • Quantitative analysis of meprin-alpha mRNA levels in inflamed intestinal mucosa.
  • Evaluation of intestinal injury and inflammation in meprin-alpha knockout mice using a dextran sulfate sodium (DSS) model.

Main Results:

  • Significant genetic associations were found between MEP1A SNPs and UC susceptibility.
  • Meprin-alpha mRNA levels were decreased in inflamed mucosa from IBD patients.
  • Meprin-alpha knockout mice showed exacerbated intestinal injury and inflammation in the DSS model.

Conclusions:

  • The MEP1A gene is implicated as a susceptibility gene for UC.
  • Decreased meprin-alpha expression is linked to intestinal inflammation in IBD patients and experimental models.

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