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Ann Rheum Dis. Nov 2003; 62(11): 1083–1087.
PMCID: PMC1754357

Endothelial nitric oxide synthase gene polymorphisms in Behçet's disease and rheumatic diseases with vasculitis


Objective: To assess potential associations between Korean Behçet's disease (BD) or other rheumatic diseases with vasculitis and two polymorphisms of the endothelial nitric oxide synthase (eNOS) gene, which include the Glu298Asp polymorphism in exon 7 and a variable number of tandem repeats (VNTR) polymorphism in intron 4.

Methods: 65 patients with BD, 27 with rheumatic diseases with vasculitis, and 80 controls were studied. Analyses of the Glu298Asp polymorphism in exon 7 and VNTR polymorphism in intron 4 of the eNOS gene were made by the polymerase chain reaction (PCR)-restriction fragment length polymorphism technique and PCR genotyping, respectively. Additionally, HLA-B51 typing was performed in the BD group and controls by a two step PCR sequence-specific primers method.

Results: Significant differences in Glu298Asp genotype frequencies were found between the BD or vasculitis groups and the controls (BD group v controls: pcorr=0.006; vasculitis group v controls: p<0.001). The Asp298 frequency was much higher in the BD and vasculitis groups than in the controls. Even after stratification of the BD group based on the results of HLA-B51 testing, a significant association of the Glu298Asp polymorphism was still found (p=0.002, Mantel-Haenszel weighted odds ratio 4.3, 95% confidence interval 1.7 to 10.9). Distribution of the genotype frequencies in two eNOS gene polymorphisms was similar in connective tissue diseases-associated vasculitis and primary vasculitic syndromes. In contrast, distribution of alleles and genotypes of VNTR polymorphism did not differ between BD or vasculitis groups and the controls.

Conclusion: The Glu298Asp polymorphism in exon 7 of the eNOS gene seems to be a susceptibility gene for Korean BD and other rheumatic diseases.

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Selected References

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Figures and Tables

Figure 1
Analysis of the Glu298Asp polymorphism in exon 7 of the eNOS gene. Three kinds of restriction fragments are shown after digestion with Ban II: lane 1, size marker; lane 2, homozygote (Asp/Asp); lane 3, homozygote (Glu/Glu) lane 4, heterozygote (Glu/Asp). ...
Figure 2
Analysis of the VNTR polymorphism in intron 4 of the eNOS gene. The band of 420 bp indicates five repeats and the band of 393 bp indicates four repeats of the 27 bp: lane 1, size marker; lane 2, wild type (4b/b); lane 3, four and five repeats heterozygote ...

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