Association of a functional inducible nitric oxide synthase promoter variant with susceptibility to biopsy-proven giant cell arteritis

OBJECTIVE: To assess the contribution of 2 polymorphisms within the inducible nitric oxide (NOS2A) promoter region to susceptibility to giant cell arteritis (GCA). METHODS: One hundred three patients with biopsy-proven GCA and 198 ethnically matched controls from the Lugo region (Northwest Spain) were studied. Patients and controls were genotyped using polymerase chain reaction techniques for a multiallelic (CCTTT)n and for the TAAA repeat polymorphism in the promoter region of the NOS2A gene. RESULTS: No significant differences in allele or genotype frequencies for the (CCTTT)n repeat polymorphism in the NOS2A gene between patients with GCA and controls were observed. However, significant differences for the TAAA repeat polymorphism between patients and controls were found. The overall distribution of NOS2A TAAA genotypes in patients with biopsy-proven GCA was significantly different than controls (p = 0.026). Patients with GCA had an increased frequency of the NOS2A TAAA+ allele (16.5%) compared with controls (9.1%) (p = 0.007; OR 1.98; 95% CI 1.20-3.27). This was due to an increased frequency of both heterozygotes (27.2%) and homozygotes (2.9%) for NOS2A TAAA+ observed in patients compared to controls (15.2% and 1.5%, respectively) (p = 0.007; OR 2.15; 95% CI 1.23-3.78). CONCLUSION: Our results suggest a potential implication for NOS2A TAAA gene polymorphism in GCA susceptibility.