Genetic variation in myosin IXB is associated with ulcerative colitis.
OBJECTIVE
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.
van Bodegraven
Adriaan A
AA
Department of Gastroenterology, VU University Medical Centre, Amsterdam, The Netherlands.
Curley
Christine R
CR
Hunt
Karen A
KA
Monsuur
Alienke J
AJ
Linskens
Ronald K
RK
Onnie
Clive M
CM
Crusius
J Bart A
JB
Annese
Vito
V
Latiano
Anna
A
Silverberg
Mark S
MS
Bitton
Alain
A
Fisher
Sheila A
SA
Steinhart
A Hilary
AH
Forbes
Alastair
A
Sanderson
Jeremy
J
Prescott
Natalie J
NJ
Strachan
David P
DP
Playford
Raymond J
RJ
Mathew
Christopher G
CG
Wijmenga
Cisca
C
Daly
Mark J
MJ
Rioux
John D
JD
van Heel
David A
DA
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002648:Child; D015331:Cohort Studies; D003093:Colitis, Ulcerative / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009218:Myosins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D044465:White People / Q000235:genetics
C113469:myosin IXB; D009218:Myosins