Drugs known as beta blockers, which antagonize the β-adrenergic receptor (β-AR), are an important component of the treatment regimen for chronic heart failure (HF). However, a significant body of evidence indicates that genetic heterogeneity at the level of the β1-AR may be a factor in explaining the variable responses of HF patients to beta blockade. In this issue of the JCI, Rochais et al. describe how a single amino acid change in β1-AR alters its structural conformation and improves its functional response to carvedilol, a beta blocker currently used in the treatment of HF (see the related article beginning on page 229). This may explain why some HF patients have better responses not only to carvedilol but to certain other beta blockers as well. The data greatly enhance our mechanistic understanding of myocardial adrenergic signaling and support the development of “tailored” or “personalized” medicine, in which specific therapies could be prescribed based on a patient’s genotype.
Brent R. DeGeorge, Walter J. Koch
The effect of the β1-AR Gly389Arg polymorphism on signal transduction and beta blockade by carvedilol.