title: High prevalence of polymorphisms of angiotensin-converting enzyme (I/D) and endothelial nitric oxide synthase (Glu298Asp) in patients with systemic sclerosis.
abstract: OBJECTIVE
  Systemic sclerosis is characterized by progressive microvascular occlusion and fibrosis and by an imbalance in the fibrinolytic system. In vivo and in vitro studies suggest that the renin-angiotensin system partly regulates vascular fibrinolytic balance. Angiotensin II increases the production and secretion of plasminogen activator inhibitor-1, while angiotensin-converting enzyme (ACE) contributes to reduced production of tissue plasminogen activator and endothelial nitric oxide synthesis by bradykinin degradation. The aim of our study was to investigate the effects of ACE insertion/deletion (I/D) and endothelial nitric oxide synthase (eNOS) Glu298Asp (G894-->T) and T-786-->C polymorphisms in patients with systemic sclerosis.
  
  
  METHODS
  We studied 73 consecutive patients (47 with limited and 26 with diffuse cutaneous systemic sclerosis) and 112 control subjects. ACE I/D and eNOS polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis.
  
  
  RESULTS
  The ACE I/D and the eNOS G894-->T polymorphisms were more common in patients than in controls (for the ACE D allele: odds ratio [OR] = 3.4; 95% confidence interval [CI]: 1.5 to 7.9; P = 0.003; for the eNOS T allele: OR = 1.9; 95% CI: 1.0 to 3.4; P = 0.04). There was no association between the eNOS T-786-->C polymorphism and systemic sclerosis.
  
  
  CONCLUSIONS
  Our findings of an increased risk of systemic sclerosis in ACE D and eNOS 894T allele carriers suggest that these polymorphisms may contribute to the pathogenesis of the disease.
authors.affiliation: Department of Medical and Surgical Critical Care, Section of Clinical Medicine and Cardiology, University of Florence, Florence, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Fatini
authors.forename: Francesca
authors.initials: F
authors.lastname: Gensini
authors.forename: Elena
authors.initials: E
authors.lastname: Sticchi
authors.forename: Beatrice
authors.initials: B
authors.lastname: Battaglini
authors.forename: Chiara
authors.initials: C
authors.lastname: Angotti
authors.forename: Maria L
authors.initials: ML
authors.lastname: Conforti
authors.forename: Sergio
authors.initials: S
authors.lastname: Generini
authors.forename: Alberto
authors.initials: A
authors.lastname: Pignone
authors.forename: Rosanna
authors.initials: R
authors.lastname: Abbate
authors.forename: Marco
authors.initials: M
authors.lastname: Matucci-Cerinic
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000235:genetics* / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000235:genetics*; D011110:Polymorphism, Genetic; D015995:Prevalence; D012306:Risk; D012595:Scleroderma, Systemic / Q000453:epidemiology* / Q000235:genetics*
chemical_list: D019001:Nitric Oxide Synthase; D007703:Peptidyl-Dipeptidase A