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Rheumatology Advance Access originally published online on September 11, 2009
Rheumatology 2009 48(11):1375-1377; doi:10.1093/rheumatology/kep292
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© The Author 2009. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Low prevalence of NOD2 SNPs in Behçet's disease suggests protective association in Caucasians

Jasper H. Kappen1, Graham R. Wallace2, Lisette Stolk3, Fernando Rivadeneira3, Andre G. Uitterlinden3, Paul L. A. van Daele1,4, Jon D. Laman4, Robert W. A. M. Kuijpers5, Goitze Seerp Baarsma6, Miles R. Stanford7, Farida Fortune8, Wafa Madanat9, Petrus Martin van Hagen1,4 and Jan A. M. van Laar1,4

1Department of Internal Medicine, Section of Clinical Immunology, Erasmus University Hospital, Rotterdam, The Netherlands, 2Academic Unit of Ophthalmology, University of Birmingham, Birmingham, UK, 3Department of Internal Medicine, 4Department of Immunology, 5Department of Ophthalmology, Erasmus University Hospital, 6Department of Ophthalmology, Eye Hospital, Rotterdam, The Netherlands, 7Clinical Ophthalmology, King's College London, 8Centre for Clinical and Diagnostic Oral Sciences, Queen Mary, University of London, London, UK and 9Jordan Hospital, Amman, Jordan.

Correspondence to: Jan A. M. van Laar, Erasmus University Medical Center, Room D-419, PO Box 2040, 3000 CA Rotterdam, The Netherlands. E-mail: j.vanlaar{at}erasmusmc.nl


  Abstract

Objective. It has been shown previously that three nucleotide-binding oligomerization domain containing 2 (NOD2) variants (Arg702Trp, Gly908Arg and Lue1007fs) are associated with Crohn's disease (CD), a disorder clinically resembling Behçet's disease (BD). We studied the frequency of these variants in BD patients.

Methods. DNA samples of 200 BD patients [59 Caucasians, 139 Middle Easterns (MEs) of Arab descent and 2 Asians] and 520 healthy controls (444 Caucasians and 76 MEs) were genotyped using a Taqman assay.

Results. Both the Arg702Trp and Leu1007fs (frameshift) variants were significantly less frequently present among BD patients compared with healthy controls (0.5 vs 5.8%; P < 1.10–5 and 0.0 vs 1.8%; P < 0.007, respectively). In the Caucasian subpopulation, Arg702Trp was significantly less frequent in the BD group as compared with the controls (P = 0.04); whereas in the ME subpopulation, a trend was observed (P < 0.06).

Conclusions. Of the three CD-associated single nucleotide polymorphisms, one of the variant NOD2 alleles, was found to be present significantly less in Caucasian BD patients.

KEY WORDS: Nucleotide-binding oligomerization domain containing 2 , Single nucleotide polymorphisms, Genetic association, Peptidoglycan, Neutrophil, NALP3

Submitted 4 March 2009; revised version accepted 11 August 2009.
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