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Genetic variation in myosin IXB is associated with ulcerative colitis.

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 x 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.

journal_name

Gastroenterology

journal_title

Gastroenterology

authors

van Bodegraven AA,Curley CR,Hunt KA,Monsuur AJ,Linskens RK,Onnie CM,Crusius JB,Annese V,Latiano A,Silverberg MS,Bitton A,Fisher SA,Steinhart AH,Forbes A,Sanderson J,Prescott NJ,Strachan DP,Playford RJ,Mathew CG,Wijm

doi

10.1053/j.gastro.2006.09.011

subject

Has Abstract

pub_date

2006-12-01 00:00:00

pages

1768-74

issue

6

eissn

0016-5085

issn

1528-0012

pii

S0016-5085(06)02005-1

journal_volume

131

pub_type

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