An Overview of Gene Variants of Endothelin-1: A Critical Regulator of Endothelial Dysfunction

Endothelial dysfunction (ED) is an early marker of development of cardiovascular diseases and is closely related to clinical events in patients with atherosclerosis and hypertension. Endothelin-1 (ET-1), a potent vasoconstrictor, and nitic oxide (NO), a potent vasodilator, produced in endothelial cells are leading molecules which regulate vascular function. Failure of the physiological balance between these two molecules, often aggravated by increased production and biological activity of ET-1, commonly reflects endothelial dysfunction. The role of endothelium-derived small molecules like ET-1 (among many) with diverse biological functions continues to fascinate researchers all over the world both for its evolutionary significance and its translational potential in disease biology. Studies on systems genetics in human endothelial cells have provided evidence supporting the possibility that predisposition to complex disease is manifested through noncoding common genetic variants that modify levels of target gene expression in endothelial cells. These studies highlight the importance genetic variants of regulatory molecules secreted by endothelial cells in health and disease. It is unlikely that a single-nucleotide polymorphism (SNP) would directly cause disease, but it would increase the genetic predisposition of individuals and can affect their responses to drugs and medications. The knowledge gained would help in the risk stratification and clinical management of patients with personalized medicine.