@article{4c6df89cfc844813b9442640b8620755,
title = "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 α-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 × 10-7) that displayed associations with UC. Moreover, meprin-α mRNA was decreased in inflamed mucosa of IBD patients. Meprin-α 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-α expression is associated with intestinal inflammation in IBD patients and in a mouse experimental model of IBD.",
author = "S. Banerjee and B. Oneda and Yap, \{L. M.\} and Jewell, \{D. P.\} and Matters, \{G. L.\} and Fitzpatrick, \{L. R.\} and F. Seibold and Sterchi, \{E. E.\} and T. Ahmad and D. Lottaz and Bond, \{J. S.\}",
note = "Funding Information: We thank Christine Valeski and Ge Jin, Penn State College of Medicine, for excellent technical assistance; Ken I. Welsh, Imperial College, London, Jeffrey Barrett, Wellcome Trust Center for Human Genetics, Oxford, and Martin Kohli, Max-Planck Institute of Psychiatry, Munich, for their advice in the analysis of the genetic association data, and Beatrice Flogerzi and Stefan M {\"u}l ler, Gastroenterology Department, University of Bern, for their help in acquiring and processing the biopsies of IBD patients. The meprin αKO vector was introduced into mouse ES cells by Thomas L. Saunders, University of Michigan Medical School Transgenic Facility. The Penn State College of Medicine Molecular Genetics Core Facility is acknowledged for help with DNA sequencing. This study was supported by NIH DK19691 (J.S.B.), the Falk Foundation (D.L.), the Foundation Johanna D {\"u}r m{\"u} l ler-Bol (D.L.), the Swiss National Science Foundation no. 3100A0.100772 (E.E.S.), and 3200BO-107527 (F.S.), and the Carlino Gift Fund from the Penn State College of Medicine (G.L.M.). S. Banerjee, G.L. Matters, L.R. Fitzpatrick, and J.S. Bond generated and characterized the meprin αKO mice and performed the studies for the experimental model of IBD; B. Oneda, F. Seibold, E.E. Sterchi, and D. Lottaz contributed to the analysis of the biopsies of IBD patients; L.M. Yap, D.A. Jewell, T. Ahmad, and D. Lottaz conducted the case – control association study for meprin-α in IBD.",
year = "2009",
doi = "10.1038/mi.2009.3",
language = "English (US)",
volume = "2",
pages = "220--231",
journal = "Mucosal Immunology",
issn = "1933-0219",
publisher = "Elsevier B.V.",
number = "3",
}