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Asthma drug effectiveness dependent on genes

By Wai Lang Chu , 19-Jun-2006

Researchers believe that the effectiveness of from a commonly used asthma medicine may be compromised by a gene variation, which is present in around 13 per cent of the city's population.

The discovery puts a valid case forward for genetic testing of this gene variation and whether it should be used in deciding routine asthma prescribing. In addition, this could be a first step towards "personalised medicine," in which genetic information will lead to the more effective use of drugs.

Researchers from the >University of Dundee found that a specific genetic variant, known as the Arg/Arg-16 variant, causes the asthma treatment salmeterol to be ineffective.

Results indicated while most patients had their asthma well controlled using salmeterol, those with the Arg/Arg-16 variant had almost double the number of asthma attacks compared to those with the other forms of this gene.

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

The findings follow US studies where the FDA had 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.

Currently, there are 5.2 million people in the UK 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.

"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 Somnath 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."

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.

Salmeterol is part of a group of drugs known as beta-agonists. These medicines are bronchodilators, or muscle relaxers, not anti-inflammatory drugs. They are used to help control moderate and severe asthma and to prevent night time symptoms. Long-acting beta-agonists are usually taken together with inhaled corticosteroid medicines.

The most effective, long-term control medicine for asthma is an inhaled corticosteroid because this medicine reduces the airway swelling that makes asthma attacks more likely.

Other long-term control medicines include, Leukotriene modifiers (montelukast, zafirlukast, and zileuton), which are used either alone to treat mild persistent asthma or together with inhaled corticosteroids to treat moderate or severe asthma.

Cromolyn and nedocromil, which are used to treat mild persistent asthma. Theophylline, which is used either alone to treat mild persistent asthma or together with inhaled corticosteroids to treat moderate persistent asthma.

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