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. Epub 2005 Nov 13.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • myosin IXB
  • Myosins

Associated data

  • RefSeq/NC_000019
  • RefSeq/NM_004145