Role of NOD2 variants in spondylarthritis

Crane, A. M., Bradbury, L., Van Heel, D. A., McGovern, D. P. B., Brophy, S., Rubin, L., Siminovitch, K. A., Wordsworth, B. P., Calin, A., & Brown, Matthew A. (2002) Role of NOD2 variants in spondylarthritis. Arthritis and Rheumatism, 46(6), pp. 1629-1633.

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Abstract

Objective.

To investigate the role of the gene NOD2 in susceptibility to, and clinical manifestations of, ankylosing spondylitis (AS).

Methods.

A case-control study of NOD2 polymorphisms known to be associated with Crohn's disease (CD) (Pro268 Ser, Arg702 Trp, GlY908 Arg, and Len1007fsinsC) was performed in 229 cases of primary AS with no diagnosed inflammatory bowel disease (IBD), 197 cases of AS associated with IBD (referred to as colitic spondylarthritis; comprising 78 with CD and 119 with ulcerative colitis [UC]), and 229 ethnically matched, healthy controls. Associations between NOD2 polymorphisms and several clinical features of AS, including disease severity assessed by questionnaire and age at spondylarthritis onset, were also investigated. Exclusion linkage mapping of chromosome 16 was performed in a separate group of 185 multicase families with AS.

Results.

An association was identified between Gly908 Arg and UC spondylarthritis (P = 0.016, odds ratio [OR] 4.6, 95% confidence interval [95% CI] 1.316), and a nonsignificant trend with a similar magnitude was observed in association with CD spondylarthritis (P = 0.08, OR 3.9, 95% CI 0.8-18). The Pro268Ser variant was inversely associated with UC spondylarthritis (P = 0.003, OR 0.55, 95% CI 0.37-0.82), but not with CD spondylarthritis. No association was demonstrated between NOD2 variants and primary AS, or between other variants of NOD2 and either UC or CD spondylarthritis. Carriage of the Pro268 Ser polymorphism was associated with greater disease activity as measured by the Bath Ankylosing Spondylitis Disease Activity Index (P = 0.002). Although patients with CD had a younger age at spondylarthritis onset than did those with UC (22.4 years versus 26.4 years; P = 0.01), no association was noted between the NOD2 variants linked with CD and age at spondylarthritis onset. In primary AS, the presence of a gene with a magnitude of association >2.0 was excluded (exclusion logarithm of odds score less than -2.0), and no association was observed with the microsatellite D16S3136.

Conclusion.

NOD2 variants do not significantly affect the risk of developing primary AS, but may influence susceptibility to, and clinical manifestations of, colitic spondylarthritis.

Impact and interest:

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ID Code: 87771
Item Type: Journal Article
Refereed: Yes
Additional Information: No file attached.
Keywords: arginine, glycine, leucine, proline, serine, tryptophan, adult, ankylosing spondylitis, article, chromosome 16, chromosome map, clinical feature, colitis, controlled study, Crohn disease, disease activity, disease association, enteritis, genetic association, genetic polymorphism, genetic susceptibility, genetic variability, human, major clinical study, onset age, priority journal, questionnaire, ulcerative colitis, Age of Onset, Carrier Proteins, Case-Control Studies, Cohort Studies, Genetic Predisposition to Disease, Genotype, Humans, Intracellular Signaling Peptides and Proteins, Lod Score, Nod2 Signaling Adaptor Protein, Polymorphism, Single Nucleotide, Proteins, Risk Factors, Spondylarthritis
DOI: 10.1002/art.10329
ISSN: 0004-3591
Divisions: Current > Schools > School of Biomedical Sciences
Current > Institutes > Institute of Health and Biomedical Innovation
Deposited On: 28 Sep 2015 06:07
Last Modified: 28 Sep 2015 06:07

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