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

Banerjee, S; Oneda, B; Yap, L M; Jewell, D P; Matters, G L; Fitzpatrick, L R; Seibold, F; Sterchi, E E; Ahmad, T; Lottaz, D; Bond, J S (2009). MEP1A allele for meprin A metalloprotease is a susceptibility gene for inflammatory bowel disease. Mucosal immunology, 2(3), pp. 220-31. New York, N.Y.: Nature Publishing Group 10.1038/mi.2009.3

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Gastroenterology
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Biochemistry and Molecular Medicine
04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Rheumatology, Clinical Immunology and Allergology

UniBE Contributor:

Seibold, Frank Werner; Sterchi, Erwin-Ernst and Lottaz, Daniel

ISSN:

1933-0219

Publisher:

Nature Publishing Group

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 15:10

Last Modified:

04 May 2014 23:22

Publisher DOI:

10.1038/mi.2009.3

PubMed ID:

19262505

Web of Science ID:

000265245600005

URI:

https://boris.unibe.ch/id/eprint/30956 (FactScience: 195332)

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