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Journal of Clinical Microbiology, March 2007, p. 968-971, Vol. 45, No. 3
0095-1137/07/$08.00+0     doi:10.1128/JCM.02062-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Testing the Interaction between NOD-2 Status and Serological Response to Mycobacterium paratuberculosis in Cases of Inflammatory Bowel Disease

Department of Internal Medicine,¹ University of Manitoba Inflammatory Bowel Disease Clinical and Research Centre, Winnipeg, Manitoba, Canada,² the Harvey M. and Lyn P. Meyerhoff Inflammatory Bowel Disease Center, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland,³ Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland,⁴ Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin⁵

Received 6 October 2006/ Accepted 11 January 2007

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 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.

Published ahead of print on 24 January 2007.