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

• Published in: Clinical and experimental rheumatology 2010-03, Vol.28 (2), p.169-175
• Main Authors: SINICI, I, KALYONCU, U, KARAHAN, S, KIRAZ, S, ATALAR, E
• Format: Article
• Language: English
• Subjects: Adult; Biological and medical sciences; Diseases of the osteoarticular system; Exons - genetics; Female; Genetic Predisposition to Disease - epidemiology; Genotype; Homozygote; Humans; Introns - genetics; Logistic Models; Male; Medical sciences; Middle Aged; Nitric Oxide Synthase Type III - genetics; Polymorphism, Genetic; Promoter Regions, Genetic - genetics; Risk Factors; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Scleroderma, Systemic - epidemiology; Scleroderma, Systemic - genetics; Tandem Repeat Sequences - genetics; Turkey - epidemiology
• ISSN: 0392-856X; 1593-098X

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. 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. 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). 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.