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: p(corr)=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.


CONCLUSIONS
The Glu298Asp polymorphism in exon 7 of the eNOS gene seems to be a susceptibility gene for Korean BD and other rheumatic diseases.
Kim
J U
JU
Department of Laboratory Medicine, Ulsan University, Kangnung, South Korea.
Chang
H K
HK
Lee
S S
SS
Kim
J W
JW
Kim
K T
KT
Lee
S W
SW
Chung
W T
WT
D000328:Adult; D001528:Behcet Syndrome / Q000235:genetics*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D015235:HLA-B Antigens / Q000032:analysis; D059949:HLA-B51 Antigen; D006801:Humans; D008297:Male; D018598:Minisatellite Repeats; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012216:Rheumatic Diseases / Q000235:genetics*; D014657:Vasculitis / Q000235:genetics
D015235:HLA-B Antigens; D059949:HLA-B51 Antigen; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III