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Mutations Linked to Asthma Drug Response


Asthmatics who are homozygous for a single gene are better off when they discontinue treatment with the most common asthma drug, albuterol, pointing to the possibility of using genetic screening as part of a prescription and treatment protocol, according to newly released findings.

The study, conducted by Elliot Israel of Brigham and Women’s Hospital, and other members of the US National Heart, Lung, and Blood Institute’s Asthma Clinical Research Network, also showed a benefit of albuterol treatment for patients having two copies of the most common allele of the gene.

Their research appears in the Oct. 23 Lancet.

“Individuals with … the arginine genotype on the beta-adrenergic receptor had a poor asthma control, including more symptoms after using Albuterol daily for several weeks,” said James Kiley, director of the NHLBI. These patients might benefit from intervention, including a decrease in a use of the drug and its replacement with “other quick release medications,” he added.

More than 2 million of about 15 million asthmatics have the “arginine” genotype, which is more prevalent in particular ethnic groups, such as African Americans, said Israel, the study’s lead author. About 5 million Americans are homozygous for the “glycine” genotype, while nearly half are heterozygous, he said. Heterozygotes may react to albuterol in an intermediate fashion, although the study did not establish this, he added.

With indications that albuterol response is genetically influenced, Israel and colleagues genotyped participants for the current prospective study, comparing the albuterol responses of two groups of 78 patients — half of them arginine homozygotes and half glycine homozygotes. “From that, you have a much more powerful study to really tell what the effect is based on that genotype, versus some other confounding factor,” said Kiley.

There is no test to determine beta-adrenergic receptor genotype outside of a research setting, said Kiley. There is also no effort underway to develop such a test “that we’re aware of,” he added. “Right now that’s going to have to be pursued by more commercially oriented organizations.”

The Beta-Adrenergic Response by Genotype, or BARGE, study is the first prospective study to relate patient genotype to asthma drug response, said Kiley. In fact, the ACRN scientists re-evaluated patients who were involved in earlier, traditional drug research to plan the prospective study. “They went back and retrospectively genotyped these individuals and found this somewhat serendipitous outcome that those that had the arg-arg genotype” had worse asthma control than participants with glycine at the same position in the beta-adrenergic receptor gene, Kiley said.

— CW


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