Testing the interaction between NOD-2 status and serological response to Mycobacterium paratuberculosis in cases of inflammatory bowel disease.
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.
Bernstein
Charles N
CN
Department of Internal Medicine, University of Manitoba Inflammatory Bowel Disease Clinical and Research Centre, Winnipeg, Manitoba, Canada. cbernst@cc.umanitoba.ca
Wang
Ming-Hsi
MH
Sargent
Michael
M
Brant
Steven R
SR
Collins
Michael T
MT
D000293:Adolescent; D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood*; D003093:Colitis, Ulcerative / Q000235:genetics / Q000276:immunology / Q000382:microbiology; D003424:Crohn Disease / Q000235:genetics / Q000276:immunology / Q000382:microbiology; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics* / Q000276:immunology* / Q000382:microbiology; D008875:Middle Aged; D009154:Mutation; D016927:Mycobacterium avium subsp. paratuberculosis / Q000276:immunology*; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics*; D010283:Paratuberculosis / Q000235:genetics / Q000276:immunology / Q000382:microbiology
D000907:Antibodies, Bacterial; D053473:Nod2 Signaling Adaptor Protein