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 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.affiliation: Department of Biochemistry & Molecular Biology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA.
authors.forename: S
authors.initials: S
authors.lastname: Banerjee
authors.forename: B
authors.initials: B
authors.lastname: Oneda
authors.forename: L M
authors.initials: LM
authors.lastname: Yap
authors.forename: D P
authors.initials: DP
authors.lastname: Jewell
authors.forename: G L
authors.initials: GL
authors.lastname: Matters
authors.forename: L R
authors.initials: LR
authors.lastname: Fitzpatrick
authors.forename: F
authors.initials: F
authors.lastname: Seibold
authors.forename: E E
authors.initials: EE
authors.lastname: Sterchi
authors.forename: T
authors.initials: T
authors.lastname: Ahmad
authors.forename: D
authors.initials: D
authors.lastname: Lottaz
authors.forename: J S
authors.initials: JS
authors.lastname: Bond
mesh_terms: D000483:Alleles; D000818:Animals; D003093:Colitis, Ulcerative / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016264:Dextran Sulfate; D020022:Genetic Predisposition to Disease; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008666:Metalloendopeptidases / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D016264:Dextran Sulfate; D008666:Metalloendopeptidases; C053833:meprin A