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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{triangledown}

Charles N. Bernstein,1,2* Ming-Hsi Wang,3,4 Michael Sargent,1,2 Steven R. Brant,3,4 and Michael T. Collins5

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.

* Corresponding author. Mailing address: John Buhler Research Centre, 804F-715 McDermot Avenue, Winnipeg, Manitoba, Canada R3E 3 P4. Phone: (204) 789-3369. Fax: (204) 789-3972. E-mail: cbernst{at}cc.umanitoba.ca.

{triangledown} Published ahead of print on 24 January 2007.

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.





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