On the hemodynamic and clinical effects of Endothelin-1 level and endothelin receptor polymorphisms in systemic sclerosis

Purpose: Scleroderma is a fibrotic condition characterized by immunological abnormalities, vascular injury and increased accumulation of extracellular matrix proteins in the skin. It has been well known that endothelin-1 has a significant role in etiology of systemic sclerosis, clinical symptoms and progression of disease. Clinical trials have led to researchers to develop new treatment modalities. It is possible that endothelin-1 level and receptor polymorphisms may influence the clinical course of disease and the therapeutic approaches. Aim of the study is to investigate the relationship between plasma level of ET-1 and the hemodynamic and clinical findings in patients with scleroderma living Çukurova Region. We also intended to analyze the incidence of ET receptor B G57S and ET receptor A -231G>A polymorphisms in patients with scleroderma and correlation between these polymorphisms and the hemodynamic and clinical findingsMethods: Forthy-three patients (2M/41F) with scleroderma and 42 healthy controls (0E/42K) were taken into the study. Enzyme-linked immunosorbent assay (ELISA) utilized to determine the ET-1 level in plasma. ET receptor B G57S and ET receptor A -231G>A polymorphisms were established by PCR-RFLP. Transthoracic echocardiography were done to scleroderma group. Twentyfour-hour Holter blood pressures measurmets were done to both groups. Respiratory function tests were also carried out. Pulmonary status was assessed by HRCTResults: Patients with scleroderma had significantly higher plasma endothelin-1 levels compared to normal subjects (p<0,001). Nevertheless, there was no correlation between plasma ET-1 level and the hemodynamic/clinical findings. Patients and the control group did not show any difference in 24-hour Holter blood pressure and pulse measurments. ET receptor B G57S polymorphism was not observed in patient and control groups, whereas there was a statistically significant difference in ET receptor A -231G>A polymorphisms between two groups (5/43 vs 0/42) respecticaly (p=0,023). We have found no association between ET receptor A -231G>A polymorphisms and plasma ET-1 levels, hemodynamic or clinical findingsConclusion: In this study, it is statistically significant increase in plasma ET-1 levels and ET receptor A -231G>A polymorphisms were found in patients with scleroderma compared to normal subjects. A relationship between plasma ET-1 levels, ET receptor A -231G>A polymorphisms and hemodynamic/clinical symptoms has not been established.Larger multicenter studies are needed to eveluate the effect of the polymorphism on the clinical findings of sclerodermaKey Words: Scleroderma, endothelin-1, endothelin receptor A -231G>A polymorphism, endothelin receptor B G57S polymorphism, Holter, echocardiography, blood pressure, pulmonary arter pressure.