Title:Polymorphism in Endothelin-1 Gene: An Overview
Volume: 11
Issue: 3
Author(s): Musa Ahmed and Abir Rghigh
Affiliation:
Keywords:
Endothelin, endothelin-1(ET-1), polymorphism, rs5370.
Abstract: 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.
