Gene variant shapes beta-blocker’s effectiveness

A medication widely used for heart failure may be most effective in people who have a common variant of a particular gene, a laboratory study suggests. Genetic testing for the variant could potentially identify patients who are most likely to benefit from the drug carvedilol, the researchers say.

Beta-blocking drugs such as carvedilol reduce the heart’s workload by blocking beta-adrenergic receptors on cells. This can protect hearts that don’t pump efficiently, such as those in people with heart failure. The primary beta-adrenergic receptor comes in several forms, the most common of which are arg389 and gly389. The majority of people have the arg389 variant.

To investigate the significance of these genetic differences, Stefan Engelhardt and his colleagues at the University of Würzburg, Germany, tested three beta-blockers, including carvedilol, on heart cells from rats that had either the arg389 or gly389 variant.

Carvedilol blocked the receptor more effectively in cells that contained the arg389 variant than in cells that contained gly389, the researchers report in the January Journal of Clinical Investigation. The effects of the two other beta-blockers didn’t depend on the form of the receptor.