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

AJ Monsuur, PIW de Bakker, BZ Alizadeh, A Zhernakova, MR Bevova, E Strengman, L Franke, R van't Slot, MJ van Belzen, ICM Lavrijsen, B Diosdado, MJ Daly, Chris J. J. Mulder, ML Mearin, Jos W. R. Meijer, Gerrit A. Meijer, E van Oort, MC Wapenaar, BPC Koeleman, C Wijmenga*

*Corresponding author voor dit werk

    Onderzoeksoutput: LetterAcademicpeer review

    215 Citaten (Scopus)

    Samenvatting

    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(1). 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(2,3). 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.

    Originele taal-2English
    Pagina's (van-tot)1341-1344
    Aantal pagina's4
    TijdschriftNature Genetics
    Volume37
    Nummer van het tijdschrift12
    DOI's
    StatusPublished - dec.-2005

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