**4. Endothelin-1 as a candidate gene in human diseases for the study of endothelial dysfunction**

Endothelin-1 like nitric oxide is a key regulator of endothelial dysfunction. The beneficial effects in maintenance of healthy endothelium are attributed to increased bioavailability of NO that regulates vascular homeostasis by causing vasodilation and by having antiproliferative, antioxidant, anti-inflammatory properties that inhibit atherogenesis. Conversely, increased synthesis of ET-1 is associated with the disturbance of homeostatic balance with pathological outcomes. The involvement of ET-1 in pathological process of vascular diseases with endothelial dysfunction like hypertension, coronary artery diseases, atherosclerosis, and diabetes is well established now. A knowledge of the mechanisms behind the development of endothelial dysfunction and the role of ET-1 and its gene is of great importance. The selection of ET-1 as a candidate gene is attractive because of its established role in vascular diseases and has assumed importance in the conduct of genetic association studies and SNP profiling in suitable population-based studies [10].
