Ser49Gly of beta1-adrenergic receptor is associated with effective beta-blocker dose in dilated cardiomyopathy.
OBJECTIVE
Our objective was to evaluate the influence of polymorphisms at codons 49 and 389 of the beta1-adrenergic receptor (beta1-AR) on the response to beta-blockers and outcome in patients with dilated cardiomyopathy.


METHODS
We genotyped both codons of the beta1-AR in 375 patients with dilated cardiomyopathy and 492 control subjects.


RESULTS
Neither of the polymorphisms was associated with susceptibility for dilated cardiomyopathy. In a retrospective analysis of patients receiving beta-blockers, there was a significant association between long-term survival rate and codon 49 (P = .014) but not codon 389 (P = .08). Despite a similar mean heart rate (69 beats/min), patients with the Ser49 genotype tended to have higher doses of beta-blockade compared with Gly49 carriers (P = .065). In patients receiving a low dose of beta-blockade (< or = 50% of targeted full dose), the 5-year mortality rate was lower among Gly49 carriers than Ser49 patients (risk ratio [RR], 0.24; 95% confidence interval [CI], 0.07-0.80; P = .020). In patients receiving high doses of beta-blockers, there was no significant difference in outcome between genotypes (P = .20), which was attributable to a better outcome for Ser49 patients treated with a high dose of beta-blockade as compared with a low dose. Gly49 carriers had a similar survival rate with different doses of beta-blockers. With low-dose beta-blockers, both codon 49 (RR, 0.26; 95% CI, 0.08-0.89; P = .029) and codon 389 (RR, 2.42; 95% CI, 1.04-5.63, P = .039) were related to 5-year mortality rate.


CONCLUSIONS
In patients with heart failure, the influence of codon 49 on the outcome and effect of beta-blockers appeared to be more pronounced than that of codon 389. The more common Ser49Ser genotype responded less beneficially to beta-blockade and would motivate genotyping to promote higher doses for the best outcome effect.
Magnusson
Yvonne
Y
Wallenberg Laboratory for Cardiovascular Research and Department of Primary Health Care, Sahlgrenska Academy at Göteborg University, Göteborg, Sweden. yvonne.magnusson@wlab.gu.se
Levin
Malin C
MC
Eggertsen
Robert
R
Nyström
Ernst
E
Mobini
Reza
R
Schaufelberger
Maria
M
Andersson
Bert
B
D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage* / Q000627:therapeutic use*; D000368:Aged; D019943:Amino Acid Substitution; D002311:Cardiomyopathy, Dilated / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D003062:Codon; D015331:Cohort Studies; D004247:DNA / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005260:Female; D005838:Genotype; D005998:Glycine; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D018342:Receptors, Adrenergic, beta-1 / Q000187:drug effects / Q000235:genetics*; D012694:Serine; D015996:Survival Rate; D016896:Treatment Outcome
D000319:Adrenergic beta-Antagonists; D003062:Codon; D018342:Receptors, Adrenergic, beta-1; D012694:Serine; D004247:DNA; D005998:Glycine