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Rheumatology Advance Access originally published online on February 10, 2005
Rheumatology 2005 44(5):614-617; doi:10.1093/rheumatology/keh561
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© The Author 2005. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oupjournals.org

Polymorphisms in the endothelial nitric oxide synthase gene are associated with Behçet's disease

J. A. Karasneh, A. H. Hajeer, A. Silman, J. Worthington, W. E. R. Ollier and A. Gul1

Arthritis Research Campaign Epidemiology Unit, University of Manchester, Manchester, UK and 1 Division of Rheumatology, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.

Correspondence to: J. Worthington, ARC Epidemiology Unit, Stopford Building, University of Manchester, Oxford Road, Manchester M13 9PT, UK. E-mail: Jane.Worthington{at}man.ac.uk

Objective. Reduced plasma nitric oxide (NO) levels in Behçet's disease (BD) patients have been implicated in the development of the endothelial abnormalities and thrombotic complications occurring in these patients. This study investigated the association of the endothelial NO Synthase (eNOS) gene polymorphisms with BD.

Methods. A case–control study was carried out using 193 unrelated Turkish BD patients and 106 healthy controls. All individuals were genotyped by PCR for two single-nucleotide polymorphisms (SNPs): –786 T->C in the promoter region and 894 G->T in exon 7 (Glu298Asp). A variable number of tandem repeats (VNTR) polymorphism in intron 4 was also investigated.

Results. The VNTR polymorphism was associated with BD, detected by an increased frequency of the b allele (odds ratio = 1.9, P = 0.0069) and b/b genotype (odds ratio = 2.2, P = 0.002) in patients. After the stratification of cases according to the family history, a significant difference between familial cases and controls in the –786 SNP was observed, with an increase in the frequency of the T allele (odds ratio = 2.5, P = 0.0016) and T/T genotype (odds ratio = 2.5, P = 0.0085), and the association of the VNTR polymorphism with BD became stronger. The –786*T and VNTR*b alleles were in linkage disequilibrium (D' = 0.65, P <0.0001), and the number of individuals homozygous for the –786*T/VNTR*b haplotype was significantly increased in the patients.

Conclusions. eNOS gene polymorphisms are associated with BD, which might contribute to the reduced NO activity observed in BD patients.

KEY WORDS: Behçet's disease, Endothelial nitric oxide synthase gene (eNOS), Single-nucleotide polymorphism, Haplotype


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[Abstract] [Full Text] [PDF]


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