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Genetic variation in myosin IXB is associated with ulcerative colitis

Citation

Van Bodegraven, AA and Curley, CR and Hunt, KA and Monsuur, AJ and Linskens, RK and Onnie, CM and Crusius, JBA and Annese, V and Latiano, A and Silverberg, MS and Bitton, A and Fisher, SA and Steinhart, AH and Forbes, A and Sanderson, J and Prescott, NJ and Strachan, DP and Playford, RJ and Mathew, CG and Wijmenga, C and Daly, MJ and Rioux, JD and van Heel, DA, Genetic variation in myosin IXB is associated with ulcerative colitis, Gastroenterology: A Journal Devoted to The Clinical and Basic Studies of The Digestive Tract and Liver, 131, (6) pp. 1768-1774. ISSN 0016-5085 (2006) [Refereed Article]

DOI: doi:10.1053/j.gastro.2006.09.011

Abstract

Background & Aims: Common germline genetic variation in the 3′ region of myosin IXB (MYO9B) has been associated recently with susceptibility to celiac disease, with a hypothesis that MYO9B variants might influence intestinal permeability. These findings suggested the current study investigating a possible further role for MYO9B variation in inflammatory bowel disease. Methods: Eight single-nucleotide polymorphisms (SNPs) were selected to tag common haplotypes from the 35-kb 3′ region of MYO9B. These included the strongest celiac disease-associated variants reported in a Dutch cohort. These SNPs were studied in 3 independently collected and genotyped case-control cohorts of European descent (UK, Dutch, and Canadian/Italian), comprising in total 2717 inflammatory bowel disease patients (1197 with Crohn's disease, 1520 with ulcerative colitis) and 4440 controls. Results: Common variation in MYO9B was associated with susceptibility to inflammatory bowel disease in all 3 cohorts examined (most associated SNP, rs1545620; meta-analysis P = 1.9 × 10-6; odds ratio, 1.2), with the same alleles showing association as reported for celiac disease. Conclusions: MYO9B genetic variants predispose to inflammatory bowel disease. Interestingly, rs1545620 is a nonsynonymous variant leading to an amino acid change (Ala1011Ser) in the third calmodulin binding IQ domain of MYO9B. Unlike previous variants (in other genes) reported to predispose to inflammatory bowel disease, the association at MYO9B was considerably stronger with ulcerative colitis, although weaker association with Crohn's disease also was observed. These data imply shared causal mechanisms underlying intestinal inflammatory diseases. © 2006 AGA Institute.

Item Details

Item Type:Refereed Article
Research Division:Medical and Health Sciences
Research Group:Clinical Sciences
Research Field:Gastroenterology and Hepatology
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Digestive System Disorders
Author:Playford, RJ (Professor Ray Playford)
ID Code:72970
Year Published:2006
Web of Science® Times Cited:71
Deposited By:Research Division
Deposited On:2011-09-05
Last Modified:2011-09-05
Downloads:0

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