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.

ABSTRACT

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.