Myosin IXB variant increases the risk of celiac disease and points toward a primary intestinal barrier defect
| Autor: | M. Luisa Mearin, Eric Strengman, Cisca Wijmenga, Erica van Oort, Behrooz Z. Alizadeh, Alexandra Zhernakova, Mark J. Daly, Begoña Diosdado, Jos W. R. Meijer, Gerrit A. Meijer, Paul I.W. de Bakker, Ineke C M Lavrijsen, Martine J. Van Belzen, Ruben van 't Slot, Marianna Bevova, Alienke J. Monsuur, Lude Franke, Martin C. Wapenaar, Chris J. J. Mulder, Bobby P. C. Koeleman |
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| Přispěvatelé: | Life Course Epidemiology, Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), Groningen Institute for Gastro Intestinal Genetics and Immunology, Transplantation Immunology Groningen, Stem Cell Aging Leukemia and Lymphoma, Arctische en Antarctische studiën |
| Rok vydání: | 2005 |
| Předmět: |
Male
Molecular Sequence Data Disease Biology Myosins Small Polymorphism Single Nucleotide Coeliac disease Myosin Intestine Small Genetics medicine Humans Genetic Predisposition to Disease Amino Acid Sequence Polymorphism Allele chemistry.chemical_classification Haplotype Intron Actin remodeling Single Nucleotide medicine.disease Gluten Introns Intestine Celiac Disease chemistry Haplotypes Immunology Female |
| Zdroj: | Nature genetics. Nature Publishing Group Nature Genetics, 37(12), 1341-1344. Nature Publishing Group |
| ISSN: | 1061-4036 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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