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Gene variation affects asthma drug treatment

Researchers at the University of Dundee have discovered that a significant proportion of young asthmatics may not benefit from a commonly used asthma medicine known as salmeterol, due to a gene variation which is present in around 13% of the population.

A research team led by Dr Somnath Mukhopadhyay, Professor Brian Lipworth and Dr Colin Palmer, has found that a specific genetic variant, known as the Arg/Arg-16 variant, causes salmeterol to be ineffective.

Their research shows that while most patients on salmeterol have their asthma well controlled, those with the Arg/Arg-16 variant have almost double the number of asthma attacks compared to those with the other forms of this gene.

Future research will determine if genetic testing for the Arg/Arg 16 variant should be used in deciding routine asthma prescribing. This is a first step in the path to "personalized medicine" where genetic information will lead to the more effective use of drugs.

"It was apparent that some patients with asthma could be failing to respond to inhaled salmeterol, but we have identified a likely cause for this that is linked to this genetic status," said Dr Mukhopadhyay, of the Children’s Asthma and Allergy Research Unit at the University.

"Where this discovery takes us is towards more personalised asthma treatment, where we can identify which medicines can be used or avoided depending on an individual’s genetic profile and we can ensure the best possible treatment."

The Arg/Arg-16 variant genetic status is reasonably common and it is present in around 13% of young people with asthma in Tayside. The Dundee team studied 546 children and adolescents with asthma in Tayside.

The findings follow studies in America where the US Food and Drug Administration, the principal food and drug regulatory organisation in the United States, has previously warned in November 2005 that salmeterol was not effective in certain individuals, especially African Americans, although the genetic status of these individuals was not studied.

Salmeterol is part of a group of drugs known as beta-agonists, and is widely prescribed within the National Health Service to patients with asthma who fail to respond well to inhaled steroids.

There are 5.2 million people in the UK currently receiving various forms of asthma treatment, and an estimated 675,000 within this population carry the Arg/Arg-16 gene variation and therefore may not benefit from salmeterol treatment.

There are other drugs that can be used as alternative treatments in these individuals.

Although genetic testing is not performed through the NHS, it is important to note that the patients who are put on salmeterol should monitor if the medicine is working or not. If asthma is still poorly controlled on salmeterol, then alternatives, rather than additional treatments, may be more useful.

The results are published today by the leading chest medical journal Thorax, published by the British Thoracic Society and the BMJ Publishing Group.

Roddy Isles | alfa
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