High prevalence of polymorphisms of angiotensin-converting enzyme (I/D) and endothelial nitric oxide synthase (Glu298Asp) in patients with systemic sclerosis.
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.
Fatini
Cinzia
C
Department of Medical and Surgical Critical Care, Section of Clinical Medicine and Cardiology, University of Florence, Florence, Italy.
Gensini
Francesca
F
Sticchi
Elena
E
Battaglini
Beatrice
B
Angotti
Chiara
C
Conforti
Maria L
ML
Generini
Sergio
S
Pignone
Alberto
A
Abbate
Rosanna
R
Matucci-Cerinic
Marco
M
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*
D019001:Nitric Oxide Synthase; D007703:Peptidyl-Dipeptidase A