Polymorphism in Endothelin-1 Gene: An Overview

Endothelin-1, (ET-1, EDN1) is an endogenous polypeptide which demonstrates dominant vasoconstriction activity and mitogenic effect. It has positive inotropic and chronotropic effects on the heart, stimulates the sympathetic and the renin-angiotensin-aldosterone systems and modifies homeostasis. The human ET-1 gene which consists of 6836 nucleotides located on chromosome 6p23-p24 produces Pre-pro-ET-1, which is consequently cleaved to big-ET-1. The mature 21-amino acid ET-1 is generated by subsequent enzymatic cleavage of the big-ET-1. A comprehensive review of the literature on the consequences of different ET-1 gene variants on ET-1 linked diseases has not been accomplished. Many variants of ET-1 gene, including transversion, transition, insertion, and repeated nucleotide polymorphisms, which influence the hereditary risk of cardiovascular and other related diseases have already been located, genotyped, and examined. Among them ten polymorphisms including transversion;-1370 (T-1370G) (rs1800541), +5665 (Lys198Asn) (rs5370), G2288T polymorphisms (rs2070699), and-974 C>A (rs3087459) polymorphism, transition; +3660 (Glu106Glu) (rs5369), G(8002) A (rs2071942), rs1476046 polymorphism, rs2071943 polymorphism, and rs9296345 polymorphism, and insertion/delete; +138 (+138/ex1ins/delA) (rs1800997) were studied and phenotyped extensively. Some significant associations with many different diseases (phenotypes) especially those related to cardiovascular system diseases such as hypertension, ischemic diseases, angina, and acute coronary syndrome have been described in the literature. Some are associated with other diseases such as asthma, pulmonary edema, hearing impairment, obesity and sleep apnea. Moreover, some are modifying the course and adverse effects of several drugs. Many of these polymorphisms were studied, thus some inner complex association manner was also described.