Study says genetic mutation alters response to heart drugs

Beta-blockers help to reduce the heart’s workload via their action on beta-adrenergic receptors present in cardiac cells. The single amino acid change in the beta1-adrenergic receptor may differ from person to person and alters the receptor’s conformation and in doing so may alter the receptor’s response to a given beta blocker.

Researchers examined variant beta1-adrenergic receptors in which the amino acid at position 389 had been replaced by either an arginine or a glycine residue. The authors were able to directly assess, in real time, the effects of 3 different beta1-adrenergic receptor antagonists bisoprolol, metoprolol, and carvedilol on the Arg389 and Gly389 variant beta1-adrenergic receptors.

They found that while each of these drugs caused a conformational change in the receptors, the effect of bisoprolol and metoprolol was minor and did not noticeably differ between the Arg389 and Gly389 receptor variants. In contrast, carvedilol treatment induced a response from the Arg389 variant that was 2.5-fold that of the Gly389 variant. This was attributed to carvedilol’s ability to induce a more extreme conformational change in the Arg389 variant of the receptor, resulting in significantly dampened cAMP signaling in cardiac cells.

An accompanying commentary also reported that the Arg389 variant is 20% less common in black patients compared with non-black patients, and this may partially explain the poorer response to beta1-adrenergic receptor antagonists seen in blacks.

Future work on genetic mutations in these receptors may eventually lead to a situation in which doctors could prescribe drug treatment that is adapted according to each patient’s own genetic makeup, said the researchers.