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INFLAMMATORY BOWEL DISEASE |
1 Institute of Cell and Molecular Science, Barts and The London, Queen Mary’s School of Medicine and Dentistry, London, UK
2 Division of Medicine, Imperial College London (Hammersmith Campus), London, UK
3 Complex Genetics Section, University Medical Centre Utrecht, the Netherlands
4 Avon Longitudinal Study of Parents and Children, University of Bristol, Bristol, UK
5 Department of Gastroenterology, Barts and the London NHS Trust, London, UK
6 Department of Gastroenterology, John Radcliffe Hospital, Oxford, UK
7 Division of Community Health Sciences, St George’s, University of London, London, UK
Correspondence to:
Correspondence to:
Professor D A van Heel
Institute of Cell and Molecular Science, Barts and The London, Queen Mary’s School of Medicine and Dentistry, Turner St, London E1 2AD; d.vanheel{at}qmul.ac.uk
Background and aims: Development of coeliac disease involves an interaction between environmental factors (especially dietary wheat, rye, and barley antigens) and genetic factors (there is strong inherited disease susceptibility). The known human leucocyte antigen (HLA)-DQ2 and -DQ8 association explains only a minority of disease heritability. A recent study in the Dutch population suggested that genetic variation in the 3' region of myosin IXB (MYO9B) predisposes to coeliac disease. MYO9B is a Rho family GTPase activating protein involved in epithelial cell cytoskeletal organisation. MYO9B is hypothesised to influence intestinal permeability and hence intestinal antigen presentation.
Methods: Four single nucleotide polymorphisms were chosen to tag all common haplotypes of the MYO9B 3' haplotype block (exons 15–27). We genotyped 375 coeliac disease cases and 1366 controls (371 healthy and 995 population based). All individuals were of White UK Caucasian ethnicity.
Results: UK healthy control and population control allele frequencies were similar for all MYO9B variants. Case control analysis showed no significant association of any variant or haplotype with coeliac disease.
Conclusions: Genetic variation in MYO9B does not have a major effect on coeliac disease susceptibility in the UK population. Differences between populations, a weaker effect size than originally described, or possibly a type I error in the Dutch study might explain these findings.
Abbreviations: HLA, human leucocyte antigen; SNP, single nucleotide polymorphism; MYO9B, gene encoding myosin IXB
Keywords: coeliac disease; myosin IXB; MYO9B
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