Endothelial nitric oxide synthase haplotype associations in biopsy-proven giant cell arteritis

Objective. To assess the influence of endothelial nitric oxide synthase (eNOS) polymorphisms in the susceptibility to giant cell arteritis (GCA). Methods. We studied 57 patients with biopsy-proven GCA diagnosed at the Rheumatology Division of Hospital Xeral-Calde and 117 ethnically matched controls. Patients and controls were genotyped by PCR for a variable number tandem repeat polymorphism in intron 4, a T/C polymorphism at position -786 in the promoter region, and a polymorphism in exon 7 (298Glu/Asp or 5557G/T) of the eNOS gene. Results. No differences in allele or genotype frequencies for individual polymorphisms were observed between patients with GCA and controls. However, when haplotype frequencies for the combination of the 3 eNOS polymorphisms were estimated, a significant increase in the frequency of haplotype C/1/T and a significant decrease in the frequency of haplotype C/1/G were observed in GCA patients compared to controls (p = 0.04, OR 1,8, 95% CI 1.0-3.3; p = 0.02, OR 0.3, 95% CI 0.1-0.8, respectively). Conclusion. Significant differences in eNOS haplotype frequencies between GCA patients and controls may indicate a role for these polymorphisms in the susceptibility to this condition.