Endothelial nitric oxide synthase gene polymorphisms in giant cell arteritis

• Published in: Arthritis and rheumatism Vol. 48; no. 11; pp. 3219 - 3223
• Main Authors: Salvarani, Carlo, Casali, Bruno, Nicoli, Davide, Farnetti, Enrico, Macchioni, Pierluigi, Catanoso, Maria Grazia, Chen, Qingquan, Bajocchi, Gianluigi, Boiardi, Luigi
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01-11-2003; Wiley
• Subjects: Aged; Aspartic Acid; Biological and medical sciences; Diseases of the osteoarticular system; DNA - analysis; DNA Mutational Analysis; Female; Gene Frequency; Genetic Predisposition to Disease; Genotype; Giant Cell Arteritis - enzymology; Giant Cell Arteritis - genetics; Glutamic Acid; Heterozygote; Humans; Male; Medical sciences; Middle Aged; Nitric Oxide Synthase - genetics; Nitric Oxide Synthase Type III; Point Mutation; Polymerase Chain Reaction; Polymorphism, Genetic; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Vascular disease; Vasculitis; Gene; Enzyme; Systemic disease; Rheumatology; Cardiovascular disease; Giant cell arteritis; Oxidoreductases; Nitric-oxide synthase; Polymorphism
• ISSN: 0004-3591; 1529-0131
• DOI: 10.1002/art.11307

Objective
To examine potential associations of the Glu/Asp298 polymorphism in exon 7 and the 4a/b polymorphism in intron 4 of the endothelial nitric oxide synthase (eNOS) gene with susceptibility to and clinical expression of giant cell arteritis (GCA), particularly in patients with versus those without ischemic complications.
Methods
Ninety‐one consecutive patients with biopsy‐proven GCA, who were residents of Reggio Emilia, Italy, and 133 population‐based controls from the same geographic area were genotyped by polymerase chain reaction and allele‐specific oligonucleotide techniques for eNOS polymorphisms in exon 7 and intron 4. The patients were separated into 2 subgroups according to the presence or absence of ischemic complications (visual loss and/or jaw claudication and/or aortic arch syndrome).
Results
The distribution of the Glu/Asp298 genotype differed significantly between GCA patients and controls (corrected P [Pcorr] = 0.003). Carriers of the Asp298 allele (Asp/Asp or Glu/Asp) were significantly more frequent among the GCA patients than among the controls (Pcorr = 0.0002, odds ratio 3.3, 95% confidence interval 1.7–6.3). The distribution of the 4a/b genotype was similar in GCA patients and controls. No significant associations were found when GCA patients with and without ischemic complications were compared.
Conclusion
Our findings show that the Glu/Asp298 polymorphism of the eNOS gene is associated with GCA susceptibility.