A polymorphism in the endothelin-A receptor gene predicts survival in patients with idiopathic dilated cardiomyopathy
| Autor: | Andreas Perrot, Reinhold Kreutz, Klaus Schmidt-Petersen, Rainer Dietz, Nana Bit-Avragim, Karl-Josef Osterziel, C. Eichhorn, Stefan-Martin Herrmann, J. Pfeifer, Martin Paul |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Cardiomyopathy
Dilated Male medicine.medical_specialty Time Factors Genotype Heart disease Adrenergic beta-Antagonists Angiotensin-Converting Enzyme Inhibitors Coronary Angiography Severity of Illness Index Gastroenterology Renin-Angiotensin System Predictive Value of Tests Internal medicine Idiopathic dilated cardiomyopathy medicine Humans Allele Alleles Aged Polymorphism Genetic Ejection fraction Receptors Endothelin business.industry Proportional hazards model Genetic Variation Stroke Volume Dilated cardiomyopathy Odds ratio Middle Aged Prognosis Receptor Endothelin A medicine.disease Receptor Endothelin B Survival Analysis Phenotype Endocrinology Echocardiography Female Cardiology and Cardiovascular Medicine Endothelin receptor business Biomarkers Follow-Up Studies |
| Zdroj: | European Heart Journal. 22:1948-1953 |
| ISSN: | 0195-668X |
| DOI: | 10.1053/euhj.2001.2626 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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