A novel polymorphism in the gene coding for the beta(1)-adrenergic receptor associated with survival in patients with heart failure

Aims The adrenergic nervous system is of major importance in congestive hea rt failure. No genetic polymorphism has previously been identified in the b eta(1)-adrenergic receptor gene. The aim of this study was to find possible mutations in this gene and to relate such findings to morbidity and progno sis in heart failure. Methods and Results Genomic DNA was extracted from blood leukocytes from pa tients with congestive heart failure (n=184) and from age-matched controls (n=77). The part of the beta(1)-adrenergic receptor gene corresponding to n ucleotide 1-255 was amplified by polymerase chain reaction and analysed by automated sequencing. The patients were investigated by echocardiography an d followed regarding symptoms and survival for 5 years. A missense mutation was identified at nucleotide position 145 in the beta(1)-adrenergic recept or gene, which predicted an amino acid substitution at position 49 (Ser49Gl y). 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 pat ients with the wild type gene and 39% of the patients with the Ser49Gly, va riant had died or had experienced hospitalization (P=0.005). Patients witho ut the mutation had significantly poorer survival compared to those with th e mutation, risk ratio 2.34(95% CI 1.30-4.20), P=0.003. In a mulivariate an alysis, the risk ratio was 2.03 (95% CI 0.99-4.16) P=0.05. Conclusion A novel missense mution in the beta, adrenergic receptor gene wa s associated with a decreased mortality risk in patients with congestive he art failure. These data suggest that the beta(1)-receptor Ser49Gly variant might be associated with altered receptor function, resulting in myocardial protection in patients with heart failure. (Eur Heart J 2000; 21: 1853-185 8, doi:10.1053/euhj,1999, 1994) (C) 2000 The European Society of Cardiology .