Myosin IXB variant increases the risk of celiac disease and points toward a primary intestinal barrier defect.

Abstract

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.

• Authors: Alienke J Monsuur, Paul I W de Bakker, Behrooz Z Alizadeh, Alexandra Zhernakova, Marianna R Bevova, Eric Strengman, Lude Franke, Ruben van't Slot, Martine J van Belzen, Ineke C M Lavrijsen, Begoña Diosdado, Mark J Daly, Chris J J Mulder, M Luisa Mearin, Jos W R Meijer, Gerrit A Meijer, Erica van Oort, Martin C Wapenaar, Bobby P C Koeleman, Cisca Wijmenga
• Journal: Nature genetics (Nat Genet) Vol. 37 Issue 12 Pg. 1341-4 (Dec 2005) ISSN: 1061-4036 [Print] United States
• PMID: 16282976 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• myosin IXB
• Myosins

Topics

• Amino Acid Sequence
• Celiac Disease (genetics, physiopathology)
• Female
• Genetic Predisposition to Disease
• Haplotypes
• Humans
• Intestine, Small (physiopathology)
• Introns (genetics)
• Male
• Molecular Sequence Data
• Myosins (genetics)
• Polymorphism, Single Nucleotide