Variations in the genes that control enzymes responsible for clearing harmful chemicals breathed into the body have been linked to the development of asthma and other respiratory diseases.

The researchers studied microsomal epoxide hydrolase (EPHX1) levels and genetic variations in gluathione S-transferase P1 (GSTP1) in more than 3000 schoolchildren who had been diagnosed with asthma.

Both EPHX1 and GSTP1 are involved in clearing the body of toxins, including polyaromatic hydrocarbons from vehicle emissions.

Children with very active EPHX1 were 1.5 times as likely to have asthma as those with low EPHX1 activity.

Those with high EPHX1 levels, who also carried a variation of the GSTP1 gene were four times as likely to have asthma.

But proximity to road traffic pollution seemed to have a key role in triggering genetic susceptibility.

Children with very active EPHX1 and living within 75 metres of a main road were more than three times as likely to have asthma as those with relatively low EPHX1 levels.

But children with one or two variations in the GSTP1 gene, and who lived close to a major road, were up to nine times as likely to have asthma as those who lived further away

The results were similar, irrespective of whether the asthma was current, had began early, or late (after the age of 3).

The authors conclude that children with high EPHX1 activity, who carry genetic variants of GSTP1 are at greater risk of developing asthma.

But the risk appears to be even greater in those who live close to main roads and are exposed to road traffic pollution, they say.

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"This finding demonstrates the critical role of gene environment interaction in determining disease susceptibility," says David A. Schwartz, M.D., director of the National Institute of Environmental Health Sciences. "The investigators at USC have identified key genetic variations in biological pathways related to PAH metabolism that are associated with the occurrence of asthma in children who live in close proximity to traffic."

Approximately 12 percent of children in the study carried both of the variations and three percent were in the highest risk group based on where they lived. However, there are a number of genes that could be linked with asthma, and researchers are just beginning to study the associations between genes and environmental factors, Salam says.

It is difficult to say that if parents with an asthmatic child move further from busy streets, the child will definitely have fewer symptoms, he explains. All that can be said at this moment is that data from this and other studies show strong evidence that living near heavy traffic increases asthma risks and exacerbates symptoms in children who already have asthma.

Funding for this study came from the National Institute of Environmental Health Sciences, the U.S. Environmental Protection Agency, the National Heart, Lung and Blood Institute, the California Air Resources Board and the Hastings Foundation.

Muhammad T. Salam, Pi-Chu Lin, Edward L. Avol, W. James Gauderman, Frank D. Gilliland, Microsomal Epoxide Hydrolase, Glutathione S-transferase P1, Traffic and Childhood Asthma. Thorax , 2007; doi: 10.1136/thx.2007.080127.

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