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European Heart Journal 2001 22(20):1948-1953; doi:10.1053/euhj.2001.2626
Copyright © 2001 by the European Society of Cardiology.
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A polymorphism in the endothelin-A receptor gene predicts survival in patients with idiopathic dilated cardiomyopathy

S.-M. Herrmanna,f1, K. Schmidt-Petersena, J. Pfeifera, A. Perrotb, N. Bit-Avragimb, C. Eichhornb, R. Dietzb, R. Kreutza, M. Paula and K.J. Osterzielb

a Institute of Clinical Pharmacology and Toxicology, Department of Clinical Pharmacology, Benjamin Franklin Medical Center, Freie Universität, Berlin, Germany
b Franz-Volhard-Klinik, Max-Delbrück-Center for Molecular Medicine, Humboldt-Universität, Berlin, Germany

revised January 30, 2001; accepted January 31, 2001

Abstract

Aims The endothelin system plays a role in the complex pathophysiology of idiopathic dilated cardiomyopathy. We investigated whether genetic polymorphisms of the endothelin system might be associated with dilated cardiomyopathy-related cardiac phenotypes and differences in disease outcome.

Methods One hundred and twenty-five unrelated dilated cardiomyopathy patients of a well characterized dilated cardiomyopathy cohort were genotyped for six common polymorphisms of the endothelin-1, endothelin-A (ETA) and endothelin-B (ETB) receptor genes using hybridization with allele-specific oligonucleotides.

Results The H323H (C/T) polymorphism in exon 6 of the ETAreceptor gene was significantly associated with a shorter survival time after diagnosis. The odds ratio for carriers of the less frequent ETAT allele to die within 2 years after diagnosis was 5·5 (95% confidence interval, 1·4 to 21·0, P=0·013) compared to non-carriers. Kaplan–Meier analysis revealed a significantly different survival time for T allele carriers as compared to non-carriers as tested by logrank (P=0·0196), Breslow (P=0·0195), and Tarone tests (P=0·020). The influence of the ETAH323H polymorphism on survival remained significant when known predictors of prognosis such as left ventricular ejection fraction, left ventricular end-diastolic diameter, age and NYHA functional classification were entered in a Cox proportional hazards analysis. In this model, end-diastolic diameter showed a trend to influence survival (P=0·07) but only the ETAH323H polymorphism (P=0·0029) was a significant independent predictor of survival.

Conclusions Our results suggest that genetic variation in the ETAreceptor predicts survival in dilated cardiomyopathy patients, which might have important consequences for the identification of high-risk individuals.

Key Words: Endothelin-A receptor, genetic polymorphism, dilative cardiomyopathy, survival

f1 Correspondence: Stefan-Martin Herrmann, Institute of Clinical Pharmacology and Toxicology, Department of Clinical Pharmacology, Benjamin Franklin Medical Center, Freie Universität Berlin, Hindenburgdamm 30, 12200 Berlin, Germany.


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