High prevalence of polymorphisms of angiotensin-converting enzyme (I/D) and endothelial nitric oxide synthase (Glu298Asp) in patients with systemic sclerosis.

PURPOSE:Systemic sclerosis is characterized by progressivemicrovascular occlusion and fibrosis and by an imbalance in thefibrinolytic system. In vivo and in vitro studies suggest that therenin-angiotensin system partly regulates vascular fibrinolyticbalance. Angiotensin II increases the production and secretionof plasminogen activator inhibitor-1, while angiotensin-con-verting enzyme (ACE) contributes to reduced production oftissue plasminogen activator and endothelial nitric oxide syn-thesis by bradykinin degradation. The aim of our study was toinvestigate the effects of ACE insertion/deletion (I/D) and en-dothelial nitric oxide synthase (eNOS) Glu298Asp (G8943T)and T–7863C polymorphisms in patients with systemic scle-rosis.SUBJECTS AND METHODS:We studied 73 consecutive pa-tients (47 with limited and 26 with diffuse cutaneous systemicsclerosis) and 112 control subjects. ACE I/D and eNOS poly-morphisms were genotyped by polymerase chain reaction–re-striction fragment length polymorphism analysis.RESULTS:The ACE I/D and the eNOS G8943T polymor-phisms were more common in patients than in controls (for theACE D allele: odds ratio [OR]3.4; 95% confidence interval[CI]: 1.5 to 7.9;P0.003; for the eNOS T allele: OR1.9; 95%CI: 1.0 to 3.4;P0.04). There was no association between theeNOS T–7863C polymorphism and systemic sclerosis.CONCLUSION:Our findings of an increased risk of systemicsclerosis in ACE D and eNOS 894T allele carriers suggest thatthese polymorphisms may contribute to the pathogenesis of thedisease.