Gene sheds light on heart drug response

US researchers have identified a genetic variation that affects a person's response to beta-blockers - drugs used to treat patients with heart failure. Scientists at the University of Cincinnati in Ohio have discovered that a tiny inherited difference in the protein targeted by beta-blockers may determine whether the drug works or not. Stephen Liggett's team looked at two versions of the beta-1 andrenergic receptor gene, known as Arg and Gly. Mice with two Arg gene types are both more susceptible to heart failure, and more responsive to beta-blockers. To see if the same was true for people, Liggett's team recruited 1040 volunteers, all affected by severe heart failure.

The team, who reported their results at the recent meeting of the American Association for the Advancement of Science (AAAS), gave a beta-blocker called bucindolol to half the participants, and a placebo to the rest. They followed the patients' progress for up to five years, and also determined their receptor gene type. Because everyone inherits two copies of the gene, one from each parent, a person can have either two Arg gene types, two Gly genes, or one of each.

The scientists found that people with two copies of the Arg receptor type benefited most from the drug, with 82 per cent surviving, compared to 65 per cent of those taking the placebo. But patients who had either one copy of each receptor type, or two copies of the Gly version did no better than the patients with two Arg receptors given the placebo. Liggett now intends to carry out a larger study, to confirm the findings. However, all patients would be given the bucindolol this time, since it would be unethical to give people with two Arg genes the placebo, says Liggett.

Liggett predicts that by 2010, it will be possible for doctors to tailor an individual's treatment according to their genes, an approach called pharmacogenetics. Speaking at the AAAS meeting, Kathleen Giacomini from the University of California said that other teams in the US are currently looking at tailored treatments for asthma, cancer, cardiovascular disease and depression.