Copyright © 2000 by the European Society of Cardiology.
A novel polymorphism in the gene coding for the beta1-adrenergic receptor associated with survival in patients with heart failure
Wallenberg Laboratory for Cardiovascular Research, Department of Cardiology, Sahlgrenska University Hospital, Göteborg, Sweden
revised October 19, 1999; accepted October 20, 1999
Abstract
Aims The adrenergic nervous system is of major importance in congestive heart failure. No genetic polymorphism has previously been identified in the beta1-adrenergic receptor gene. The aim of this study was to find possible mutations in this gene and to relate such findings to morbidity and prognosis in heart failure.
Methods and Results Genomic DNA was extracted from blood leukocytes from patients with congestive heart failure (n=184) and from age-matched controls (n=77). The part of the beta1-adrenergic receptor gene corresponding to nucleotide 1–255 was amplified by polymerase chain reaction and analysed by automated sequencing. The patients were investigated by echocardiography and followed regarding symptoms and survival for 5 years. A missense mutation was identified at nucleotide position 145 in the beta1-adrenergic receptor gene, which predicted an amino acid substitution at position 49 (Ser49Gly). The allele frequency of the Gly49 variant was 0·13 in controls and 0·18 in patients (P=0·19). At the time of the 5-years follow-up, 62% of the patients with the wild type gene and 39% of the patients with the Ser49Gly variant had died or had experienced hospitalization (P=0·005). Patients without the mutation had significantly poorer survival compared to those with the mutation, risk ratio 2·34 (95% CI 1·30–4·20), P=0·003. In a mulivariate analysis, the risk ratio was 2·03 (95% CI 0·99–4·16)P =0·05.
Conclusion A novel missense mution in the beta1-adrenergic receptor gene was associated with a decreased mortality risk in patients with congestive heart failure. These data suggest that the beta1-receptor Ser49Gly variant might be associated with altered receptor function, resulting in myocardial protection in patients with heart failure.
Key Words: Polymorphism (genetics), receptors, adrenergic, beta1, prognosis, congestive heart failure, congestive cardiomyopathy, hospitalization
f1 Correspondence: Dr Bert Andersson, Dept of Cardiology, Sahlgrenska University Hospital, S-413 45 Göteborg, Sweden.
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