MEP1A allele for meprin A metalloprotease is a susceptibility gene for inflammatory bowel disease.
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.
Banerjee
S
S
Department of Biochemistry & Molecular Biology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA.
Oneda
B
B
Yap
L M
LM
Jewell
D P
DP
Matters
G L
GL
Fitzpatrick
L R
LR
Seibold
F
F
Sterchi
E E
EE
Ahmad
T
T
Lottaz
D
D
Bond
J S
JS
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
D012333:RNA, Messenger; D016264:Dextran Sulfate; D008666:Metalloendopeptidases; C053833:meprin A