Endothelial nitric oxide gene polymorphism and risk of systemic sclerosis: predisposition effect of T-786C promoter and protective effect of 27 bp repeats in Intron 4.

OBJECTIVES An impaired availability of nitric oxide (NO), related to polymorphisms in endothelial nitric oxide synthase (eNOS) gene, may influence the microvasculature in systemic Sclerosis (SSc). Three potential eNOS gene polymorphisms [tandem 27-bp repeats (VNTR) in intron 4, T786C in promoter region and G894T in exon 7] were investigated to affect the susceptibility to and the clinical course of SSc. METHODS Fifty-nine patients with SSc (mean age 47,1+/-12,1 years) and 83 control subjects (mean age 41,1+/-12,8 years) were studied. Genotypes were determined through PCR with or without RFLP. RESULTS Genotype distribution was significantly different between SSc patients and controls for intron 4aa (alleles for four repeats), genotype frequency being 3.4% and 17.1%, respectively (odds ratio for dominant effect, 0.35; 95% CI, 0.17 to 0.78; p=0.004). The CC genotype of the promoter was significantly high in frequency in the SSc patients (16.9%) compared to controls (7.3%) (odds ratio for dominant effect, 2.26; 95% CI: 1.14 to 4.48; p=0.020). CONCLUSIONS Intron 4 aa genotype of eNOS gene is protective and homozygosity (CC) of T-786C promoter region is a risk factor for SSc in Turkish population. Our results highlight a possible mechanism by which a potential reduced availability of NO, related to VNTR in intron 4 and T-786C promoter polymorphism, may influence the predisposition to SSc.