Testing the interaction between NOD-2 status and serological response to Mycobacterium paratuberculosis in cases of inflammatory bowel disease

J Clin Microbiol. 2007 Mar;45(3):968-71. doi: 10.1128/JCM.02062-06. Epub 2007 Jan 24.

Abstract

In a population-based case-control study we have previously shown that 14% of healthy Manitobans carry one or two mutations in the NOD-2 locus, a gene highly associated with Crohn's disease (CD). The NOD-2 protein is the receptor responsible for recognition of bacterial peptidoglycans, and it is plausible that NOD-2 is involved in the recognition of mycobacteria. Thirty-seven percent of Manitobans with CD had >or=1 NOD-2 mutation, leading to a threefold increased risk of CD for single-mutant carriers and a 30-fold increased risk for double-mutant carriers. In the same population groups, we assessed the seroprevalence for Mycobacterium paratuberculosis and found it to be 35%, with no differences between CD, ulcerative colitis (UC), and controls. Because of high rates of CD and UC in Manitoba, we assessed whether there was an interaction between carrying a NOD-2 mutation and M. paratuberculosis seropositivity. An enzyme-linked immunosorbent assay for serum antibodies to M. paratuberculosis in cattle was adapted for human use. DNA was purified from whole blood. Subjects were genotyped for three NOD-2 variants, G908R, Cins1007fs, and R702W. Multivariate logistic regression analysis showed that NOD-2 gene mutations significantly associated with CD, but M. paratuberculosis serology did not. Furthermore, there was no interaction between NOD-2 mutation status and M. paratuberculosis serology status. For those with the NOD-2 mutation, the likelihood of CD subjects having positive M. paratuberculosis serology was similar to that of controls (odds ratio, 1.31; 95% confidence interval, 0.55-3.11). No interaction could be proven for UC or by combining CD and UC compared to controls. In conclusion, we could not find an interaction between the NOD-2 genotype and M. paratuberculosis serology in relationship to CD or UC.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Bacterial / blood*
  • Colitis, Ulcerative / genetics
  • Colitis, Ulcerative / immunology
  • Colitis, Ulcerative / microbiology
  • Crohn Disease / genetics
  • Crohn Disease / immunology
  • Crohn Disease / microbiology
  • Humans
  • Inflammatory Bowel Diseases / genetics*
  • Inflammatory Bowel Diseases / immunology*
  • Inflammatory Bowel Diseases / microbiology
  • Middle Aged
  • Mutation*
  • Mycobacterium avium subsp. paratuberculosis / immunology*
  • Nod2 Signaling Adaptor Protein / genetics*
  • Paratuberculosis / genetics
  • Paratuberculosis / immunology
  • Paratuberculosis / microbiology

Substances

  • Antibodies, Bacterial
  • Nod2 Signaling Adaptor Protein