Endothelial Nitric Oxide Synthase Gene Polymorphisms in Giant Cell Arteritis

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 [P_corr] = 0.003). Carriers of the Asp²⁹⁸ allele (Asp/Asp or Glu/Asp) were significantly more frequent among the GCA patients than among the controls (P_corr = 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.