Endothelin-1 Gene Polymorphism in Patients with Malignant Arrhythmias

Abstract

The endothelins are peptides with vasoconstricting and growth-promoting properties. Endothelin-1 (ET-1) is known with its direct positive inotropic and chronotropic effects on isolated heart and with growth effects. The aim of this pilot study was to investigate the frequency distribution of the common polymorphism of the ET-1 gene and its possible relation with hemodynamic consequences of malignant ventricular arrhythmias in patients with structural heart disease. We studied 26 consecutive patients with malignant ventricular arrhythmias and implantable cardioverterdefibrillators with a mean age of 62.7 +/- 12.2 years and a mean left ventricular ejection fraction of 0.37 +/- 11.0. Taq polymorphism of ET-1 was detected using our original polymerase chain reaction method. The polymerase chain reaction product with a length of 358 basepairs (bp) (primers 5'-CAA ACC GAT GTC CTC TGT A-3' and 5'-ACC AAA CAC ATT TCC CTA TT-3') in its non-mutated form contains a target sequence for TaqI restrictive enzyme, while a mutated product loses this cleavage site. Of 26 patients, nine (34%) had recurrent palpitations and eight (30.8%) had syncopes during their malignant arrhythmias. Nineteen patients were given amiodarone after implantable cardioverter-defibrillator insertion and seven were not treated with amiodarone. Fifteen patients had (++), 11 (+-) and 0 (- -) ET-1 genotype. The risk for syncopes was associated with the (++) genotype of the ET-1 gene (P = 0.01). Patients receiving amiodarone had significantly higher frequency of the (++) genotype (P = 0.011). All our results indicate that the presence of the ET-1 genotype (++) in patients with structural heart disease, severe left ventricular dysfunction and malignant ventricular arrhythmias increases the risk for these patients of hemodynamic collapse during these arrhythmias.

The association between endothelin‐1 gene polymorphisms and susceptibility to vitiligo in a Korean population

“…The endothelin‐1 gene (EDN1) contains five exons, is located on chromosome 6p23‐p24 distal to the human leukocyte antigen (HLA) region defined by HLA‐A, HLA‐B and DRB1, and is closely linked to D6S89. Several polymorphisms in this gene have been identified (7). The value of this study is that it analyzes the association between EDN1 polymorphisms and vitiligo.…”

“…Endothelin‐1, a potent vasoconstrictor peptide expressed in vascular endothelial cells, has been implicated in several diseases, including hypertension, atherosclerosis, malignant arrhythmia and chronic heart failure (5–8). It is produced by various somatic cells, including keratinocytes (9).…”

Gender‐specific association between preproendothelin‐1 genotype and reduction of systolic blood pressure during antihypertensive treatment‐‐‐results from the Swedish irbesartan left ventricular hypertrophy investigation versus atenolol (SILVHIA)

“…In the heart, ECE is expressed in the endocardium and myocardium. 4 PreproET-1 mRNA is expressed by human cardiomyocytes and interstitial cells that synthesize and secrete mature ET-1. 5,6 Both ET A -and ET B -receptors are present in the human myocardium.…”

The Lack of Relationship between an Endothelin-1 Gene Polymorphism (Ala288Ser) and Incidence of Hypertension: A Retrospective Cohort Study among Japanese Workers

“…6,[13][14][15][16][17][18] Moreover, the relationship between a polymorphism in the ET-1 gene and ventricular arrhythmia has been reported. 19 Although the presence of a novel polymorphism, the G/T polymorphism with an amino acid substitution (Ala to Ser) at codon 288 in exon 5 at position 862 of the ET-1 gene (Ala288Ser), was released, 20 the prevalence of the polymorphism among general population was not available. In this way, the presence of a novel human ET-1 gene polymorphism was revealed, but the relationship between the polymorphism and hypertension was not available.…”