Myosin IXb variants and their pivotal role in maintaining the intestinal barrier: A study in Crohn's disease

Matthias Prager, Tahir Durmus, Janine Büttner, Tamas Molnar, Dirk J. De Jong, Joost PH Drenth, Daniel C. Baumgart, Andreas Sturm, Klaudia Farkas, Heiko Witt, Carsten Büning

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Background. Myosin IXb (MYO9B) is involved in the regulation of epithelial barrier function. We hypothesized that MYO9B variants are associated with increased intestinal permeability measured in patients with Crohn's disease (CD), where barrier dysfunction is crucially involved in disease development. Methods. We sequenced MYO9B and genotyped five MYO9B variants (rs1545620, rs1457092, rs2279003, rs2305764 and rs2279002) and correlated these data to measurement of intestinal permeability in German CD patients (n = 122) obtained by standard oral sugar test using the lactulose/mannitol ratio after measurement of urinary excretion. We furthermore studied MYO9B variants in three European cohorts with inflammatory bowel disease (IBD) and healthy controls : Germany (CD = 264; ulcerative colitis = 143 [UC]; HC = 372); Hungary (CD = 147; UC = 117; HC = 195), the Netherlands (CD = 157; HC = 219). Results. We found an association for four studied MYO9B variants to an increased intestinal permeability in CD patients (rs1545620, p = 0.010; rs1457092, p = 0.024; rs2279003, p = 0.003; rs2305764, p = 0.015). Furthermore, we observed significantly higher absolute values of intestinal permeability for individuals carrying risk alleles within MYO9B. Looking for an overall disease association, only the rs2305764 variant was associated with CD in the Dutch cohort (p = 0.004), but not in the German or Hungarian cohort. No association to UC or a distinct phenotype in both CD and UC patients was observed for all studied MYO9B variants. Conclusion. Our data suggest a link between MYO9B variants to an increased intestinal permeability in CD patients. This supports the influence of Myosin IXb on the integrity of the epithelial barrier. The role of MYO9B variants in the overall susceptibility to IBD, however, remains to be elucidated.

Original languageEnglish
Pages (from-to)1191-1200
Number of pages10
JournalScandinavian Journal of Gastroenterology
Volume49
Issue number10
DOIs
StatePublished - 1 Oct 2014
Externally publishedYes

Keywords

  • Crohn's disease
  • Inflammatory bowel disease
  • Intestinal permeability
  • Myosin IXb
  • Ulcerative colitis

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