A polymorphism in the endothelin-A receptor gene predicts survival in patients with idiopathic dilated cardiomyopathy

Aims The endothelin system plays a role in the complex pathophysiology of i diopathic dilated cardiomyopathy. We investigated whether genetic polymorph isms of the endothelin system might be associated with dilated cardiomyopat hy-related cardiac phenotypes and differences in disease outcome. Methods One hundred and twenty-five unrelated dilated cardiomyopathy patien ts of a well characterized dilated cardiomyopathy cohort were genotyped for six common polymorphisms of the endothelin-1, endothelin-A (ETA) and endot helin-B (ETB) receptor genes using hybridization with allele-specific oligo nucleotides. Results The H323H (C/T) polymorphism in exon 6 of the ETA receptor gene was significantly associated with a shorter survival time after diagnosis. The odds ratio for carriers of the less frequent ETA T allele to die within 2 years after diagnosis was 5-5 (95% confidence interval, 1.4 to 21.0, P=0.01 3) 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 ETA H323H polymorphism on survival remained sign ificant when known predictors of prognosis such as left ventricular ejectio n fraction, left ventricular end-diastolic diameter, age and NYHA functiona l classification were entered in a Cox proportional hazards analysis. In th is model, end-diastolic diameter showed a trend to influence survival (P=0. 07) but only the ETA H323H polymorphism (P=0.0029) was a significant indepe ndent predictor of survival. Conclusions Our results suggest that genetic variation in the ETA receptor predicts survival in dilated cardiomyopathy patients. which might have impo rtant consequences for the identification of high-risk individuals. (C) 200 1 The European Society of Cardiology.