RGD Reference Report - A polymorphism in the endothelin-A receptor gene predicts survival in patients with idiopathic dilated cardiomyopathy. - Rat Genome Database

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

Authors: Herrmann, S  Schmidt-Petersen, K  Pfeifer, J  Perrot, A  Bit-Avragim, N  Eichhorn, C  Dietz, R  Kreutz, R  Paul, M  Osterziel, KJ 
Citation: Herrmann S, etal., Eur Heart J. 2001 Oct;22(20):1948-53.
RGD ID: 1580947
Pubmed: PMID:11601839   (View Abstract at PubMed)
DOI: DOI:10.1053/euhj.2001.2626   (Journal Full-text)

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 ETA receptor gene was significantly associated with a shorter survival time after diagnosis. The odds ratio for carriers of the less frequent ET(A)T 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 ETA H323H 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 ETA H323H polymorphism (P=0.0029) was a significant independent predictor of survival. CONCLUSIONS: Our results suggest that genetic variation in the ETA receptor predicts survival in dilated cardiomyopathy patients, which might have important consequences for the identification of high-risk individuals.



Objects referenced in this article
Gene EDNRA endothelin receptor type A Homo sapiens
Gene Ednra endothelin receptor type A Mus musculus
Gene Ednra endothelin receptor type A Rattus norvegicus

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