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15 May 2002

Endothelin-1 gene polymorphism in the identification of patients at risk for malignant ventricular arrhythmia.

Lýdie Izákovicova Hollá, Milan Kozák, Lýdie Izákovicova Hollá, Lubomír Krivan, Anna Vasků, Milan Sepsi, Semrád Borivoj, Jirí Vácha

Med Sci Monit 2002; 8(5): BR164-167 :: ID: 420852

Abstract

BACKGROUND: The endothelins are peptides with vasoconstricting and growth-promotingproperties. Endothelin-1 (ET-1) is known for its direct positive inotropic and chronotropic effects onisolated heart, and for growth effects. The aim of this pilot study was to investigate the frequencydistribution of a common polymorphism of the endothelin (ET-1) gene and its possible relation to thehemodynamic consequences of malignant ventricular arrhythmia in patients with structural heart disease.MATERIAL/METHODS: We studied 26 consecutive patients with malignant ventricular arrhythmia and implantablecardioverter defibrillators (ICD), mean age 62.7 +/- 12.2 years, mean LVEF 0.37 +/- 11. The Taq polymorphismof ET-1 was detected using our original PCR method. The PCR product with a length of 358 bp in its non-mutatedform contains a target sequence for the TaqI restrictive enzyme, while the mutated product loses thiscleavage site. RESULTS: Out of the 26 patients, 9 (34%) had recurrent palpitations and 8 (30.8%) hadsyncopes during their malignant arrhythmic episodes. 19 of the patients were receiving amiodarone afterICD implantation, 7 were not. 15 patients had the (++) and 11 had the (+ -) ET-1 genotype; none had the(- -) genotype. The risk of syncopes was associated with the (++) genotype (p=0.01). Patients with amiodaronehad a significantly higher frequency of the (++) genotype (p=0.011). CONCLUSIONS: All our results suggestedthat the presence of the (++)ET-1 genotype in patients with structural heart disease, severe left ventriculardysfunction, and malignant ventricular arrhythmia put these patients at a higher risk of hemodynamiccollapse during arrhythmic episodes.

Keywords: Arrhythmia, Endothelin-1, Genotype, Hemodynamic Processes, Heterozygote, Homozygote, Pilot Projects, Polymerase Chain Reaction, Polymorphism, Genetic

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Medical Science Monitor eISSN: 1643-3750