Myosin IXB variant increases the risk of celiac disease and points toward a primary intestinal barrier defect.
Celiac disease is probably the best-understood immune-related disorder. The disease presents in the small intestine and results from the interplay between multiple genes and gluten, the triggering environmental factor. Although HLA class II genes explain 40% of the heritable risk, non-HLA genes accounting for most of the familial clustering have not yet been identified. Here we report significant and replicable association (P = 2.1 x 10(-6)) to a common variant located in intron 28 of the gene myosin IXB (MYO9B), which encodes an unconventional myosin molecule that has a role in actin remodeling of epithelial enterocytes. Individuals homozygous with respect to the at-risk allele have a 2.3-times higher risk of celiac disease (P = 1.55 x 10(-5)). This result is suggestive of a primary impairment of the intestinal barrier in the etiology of celiac disease, which may explain why immunogenic gluten peptides are able to pass through the epithelial barrier.
Monsuur
Alienke J
AJ
Complex Genetics Section, DBG-Department of Medical Genetics, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, the Netherlands.
de Bakker
Paul I W
PI
Alizadeh
Behrooz Z
BZ
Zhernakova
Alexandra
A
Bevova
Marianna R
MR
Strengman
Eric
E
Franke
Lude
L
van't Slot
Ruben
R
van Belzen
Martine J
MJ
Lavrijsen
Ineke C M
IC
Diosdado
Begoña
B
Daly
Mark J
MJ
Mulder
Chris J J
CJ
Mearin
M Luisa
ML
Meijer
Jos W R
JW
Meijer
Gerrit A
GA
van Oort
Erica
E
Wapenaar
Martin C
MC
Koeleman
Bobby P C
BP
Wijmenga
Cisca
C
D000595:Amino Acid Sequence; D002446:Celiac Disease / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007421:Intestine, Small / Q000503:physiopathology; D007438:Introns / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D009218:Myosins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
C113469:myosin IXB; D009218:Myosins