Polymorphisms of Adrenergic Receptors and the Risk of Heart Failure

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Abstract
The interesting study by Small et al. (Oct. 10 issue)1 showed that two potentially synergistic adrenergic-receptor polymorphisms are associated with a risk of congestive heart failure. Since this may indeed give rise to genotype-targeted intervention studies, one important point deserves attention. Although the polymorphism involving the substitution of glycine for arginine at position 389 (Arg389Gly) of the β1-adrenergic receptor has clearly been shown to be functional in vitro, data on its consequences in vivo are conflicting.2 Moreover, there is high sequence variability in the gene encoding the β1-adrenergic receptor, with at least 18 single-nucleotide polymorphisms leading to seven amino acid exchanges.3 Thus, Arg389Gly is but one variation of the gene. Another polymorphism in the extracellular amino terminal, one involving the substitution of glycine for serine at position 49 (Ser49Gly), has been shown to affect receptor sensitivity and down-regulation to agonists in vitro,4 resting heart rate in persons with hypertension,5 and the risk of death in persons with congestive heart failure.6