Background Vascular dysfunction usually is observed before clinically detectable fibrosis of systemic sclerosis (SSc). The eNOS catalyses the synthesis of nitric oxide (NO), which maintains basal vascular tone and endothelial function. Abnormal production of e-NOS and/or iNOS impairs NO availability causing vascular disease. Genetic polymorphism may participatein these alterations.
Objectives To investigate vascular differences associated to polymorphisms T-786C and G894T of the eNOS gene on differential expression of eNOS/iNOS in the skin and vascular Duplex Sonography parameters 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 included 180 age-matched healthy volunteers. For the eNOS/iNOS skin expression we included 31 patients (14 lcSSc and 17 dcSSc).
Results In lcSSc: T-786C prevalence was TT65.5%, TC30.2% and CC4.3% (OR 1.8, IC 0.4–7.9 associated to SSc); and the G894T prevalence was GT74.3%, GT20.3% and TT5.4% (OR 1.94, IC 0.54–7.04 associated to SSc). In dcSSc: the T-786C prevalence was TT76.6%, TC20%, and CC3.3%, and G894T polymorphism was GT 82%, GT 18% and TT 0% withoutassociation with SSc. In control group: the prevalence of T-786C polymorphism was TT68.45%, TC29.4%, and CC2.22%; for G894T polymorphismwas GG74.1%, GT23.02%, TT2.87%. 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 and 1.36+/-0.7 in skin of volunteers of control+group. Left brachial intima-media thickness was statistically significantly greater in allelic variants of eNOS in SSc (p=0.025).
Conclusions In the skin of both subtypes of systemic sclerosis, the relative expression of eNOS and iNOS is increased. Genetic polymorphisms of eNOS is associated with anormal intima-media thicknes in SSc patients.
Disclosure of Interest None Declared