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

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

Affiliation

  • 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.

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