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

  • Nat Genet. 2005 Dec;37(12):1341-4. doi: 10.1038/ng1680.
Alienke J Monsuur  1 ,  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
Affiliations
  • 1. Complex Genetics Section, DBG-Department of Medical Genetics, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, the Netherlands.
PMID: 16282976 DOI: 10.1038/ng1680
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.