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Ser49Gly of β 1 ‐adrenergic receptor is associated with effective β‐blocker dose in dilated cardiomyopathy
Author(s) -
Magnusson Yvonne,
Levin Malin C.,
Eggertsen Robert,
Nyström Ernst,
Mobini Reza,
Schaufelberger Maria,
Andersson Bert
Publication year - 2005
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2005.06.004
Subject(s) - medicine , dilated cardiomyopathy , blockade , confidence interval , genotype , cardiomyopathy , beta (programming language) , heart rate , gastroenterology , cardiology , endocrinology , receptor , heart failure , blood pressure , biology , genetics , gene , computer science , programming language
Objective Our objective was to evaluate the influence of polymorphisms at codons 49 and 389 of the β 1 ‐adrenergic receptor (β 1 ‐AR) on the response to β‐blockers and outcome in patients with dilated cardiomyopathy. Methods We genotyped both codons of the β 1 ‐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 β‐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 β‐blockade compared with Gly49 carriers ( P = .065). In patients receiving a low dose of β‐blockade (≤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 β‐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 β‐blockade as compared with a low dose. Gly49 carriers had a similar survival rate with different doses of β‐blockers. With low‐dose β‐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. Conclusion In patients with heart failure, the influence of codon 49 on the outcome and effect of β‐blockers appeared to be more pronounced than that of codon 389. The more common Ser49Ser genotype responded less beneficially to β‐blockade and would motivate genotyping to promote higher doses for the best outcome effect. Clinical Pharmacology & Therapeutics (2005) 78 , 221–231; doi: 10.1016/j.clpt.2005.06.004