Gene defects in young present serious risk from environmental tobacco smoke

Chronic exposure to second-hand tobacco smoke causes some children and adolescents to go on to develop serious chest problems like asthma, while others do not appear to be particularly affected.

The researchers, within the University of Dundee Medical School, believe they have discovered why only some people develop these problems. They have identified gene defects that increase the risk of developing asthma, and worsen lung function in patients with asthma, when exposed to tobacco smoke in the environment.

Dr. Somnath Mukhopadhyay, consultant paediatrician at the Children’s Asthma and Allergy Unit within Tayside Children’s Hospital, and Dr. Colin Palmer, a molecular geneticist at the Biomedical Research Centre, studied 600 children and adolescents with asthma attending GP surgeries and hospitals within Tayside.

They checked airway peak flows, using a simple blowing test, and studied genes that help eliminate inhaled toxins.

The genes that they studied help the body produce an enzyme called glutathione-S-transferase (GST), which is particularly effective in detoxifying inhaled tobacco smoke within the lungs.

However, the genes which produce GST are subject to two common defects, one of which is present in around 50% of the population with the other occurring in around 12% of the population.

The researchers found that Scottish children who have either of the two defects in the GST genes are more susceptible to asthma associated with environmental tobacco smoke exposure than those with more intact GST status.

The researchers also found that teenagers with asthma had 15% lower peak flows if they had one of the GST gene defects and were exposed to tobacco smoke, compared to asthmatic teenagers with intact gene status.

“There is a risk that these children and teenagers, naturally unaware of their susceptible status resulting from this gene defect, could be undergoing a silent, long-standing decline in lung function over the years,” said Dr Mukhopadhyay.

“This can lead to greater risk of chronic obstructive lung disease, or COPD, in later life.”

Scotland has the highest prevalence of teenage asthma in the world. Scots also have the highest death rate in the UK for COPD, a disease that results in numerous hospital admissions and one death every two hours in the Scottish population.

The two defects in the GST genes have defined a high-risk population of young Scottish asthmatics in whom tobacco smoke is particularly harmful. The researchers say early identification of these gene defects, with concurrent strategies targeted at the protection of the high-risk population, may be effective in the long term in reducing the prevalence of asthma in Scotland. At present there is no screening for these gene defects.

The findings of the Dundee team are published in the August 6th, 2006, issue of Pediatrics, the world’s top impact factor journal for children’s medicine and the official mouthpiece for the American Academy of Pediatrics.