Background Vascular dysfunction usually preceds clinically detectable fibrosis of systemic sclerosis (SSc). Vascular affection occurs more frequently in limited subtype of SSc (lcSSc) than diffuse subtype (dcSSc). The eNOS catalyses the synthesis of nitricoxide (NO), which maintains basal vascular tone andendothelial function. Abnormal production of e-NOS and/or iNOS impairs NO availability causing disease
Objectives To investigate the prevalence of polymorphisms T-786C and G894T of the eNOS gene and the differential expression of eNOS/iNOS in the skin of SSc patients.
Methods We included 139 consecutive SSc patients. The genotyping of T-786C and G894T polymorphisms of eNOS gene was performed by Polymerase Chain Reaction Real-Time Assay. The control group comprised 180 age-matched healthy volunteers. For the eNOS/iNOS skin expression we included 31 patients (14 lcSSc and 17 dcSSc).
Results Revalence of scleroderma was 53.2% lcSSc (74/139) and46.7% (65/139) dsSSc. In control group: the prevalenceof T-786C polymorphismwas TT 68.45%, TC 29.4%, andCC2.22%;for G894T polymorphism was GG 74.1%, GT 23.02%, TT 2.87%.In lcSSc: T-786Cprevalence was TT 65.5%, TC 30.2% and CC 4.3% (OR 1.8, IC 0.4-7.9 associated to SSc); and the G894T prevalencewas GT 74.3%, GT 20.3% and TT 5.4% (OR 1.94, IC 0.54-7.04 associated to SSc).In dcSSc: the T-786Cprevalence was TT 76.6%, TC 20%, and CC 3.3%, and G894Tpolymorphism was GT 82%, GT 18% and TT 0% without association with SSc.The mean relative expression of eNOS was 10.17±15.5 and iNOS of 7.6±13.05 in lcSSc. For dcSSc the mean relative expression of eNOS was 1.74±1.16 and iNOS of 2.1±2.5. 1.08±0.3 y 1.36±0.7 in skin of volunteers of control group.
Conclusions Genetic polymorphisms of eNOS were not arisk forpresenting systemic sclerosis in this sample.In the skin of both subtypes of systemic sclerosis, the relative expression of eNOS and iNOS is increased. However this increase was more meaningful in the lcSSc subtype of the disease.
Kahaleh B. vascular disease in scleroderma: mechanisms of vascular injury. Rheum Dis Clin North Am 2008;34:57-71.
A. Dooley, S. Y. Low, A. Holmes, A. G. Kidane, D. J. Abraham, C. M. Black, and K. R. Bruckdorfer Nitric oxide synthase expression and activity in the tight-skin mouse model of fibrosis Rheumatology, 2008; 47: 272 - 280.
Disclosure of Interest None Declared
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