Genes that regulate allergic response to diesel fumes

Main Category: Respiratory / Asthma
Article Date: 09 Jan 2004 - 0:00 PDT

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Contact: Paul Williams
pwilliams@niaid.nih.gov
301-402-1663
NIH/National Institute of Allergy and Infectious Diseases (USA)

The risk of developing respiratory allergies from exposure to diesel emissions depends largely on genetics, according to a study funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH).

Given their findings, researchers estimate that up to 50 percent of the United States population could be in jeopardy of experiencing health problems related to air pollution. The study is published in the Jan. 10 issue of the British journal The Lancet.

'This important study adds to previous data that suggest how modern environmental factors interact with the body's defenses to produce 'airway' diseases considered rare before the advent of industrialized society,' says Anthony S. Fauci, M.D., director of NIAID.

'The knowledge provided by this work will help us identify people who are susceptible to the deleterious effects of diesel emissions on the clinical course of asthma and hay fever,' says Kenneth Adams, Ph.D., who oversees asthma research funded by NIAID. 'It will also help accelerate development of drugs to treat and prevent these diseases.'

This study also received support from the National Institute of Environmental Health Sciences, another NIH component.

The authors of the study examined how a family of antioxidant-related genes--GSTM1, GSTT1 and GSTP1--reacts to diesel exhaust particles, a common air pollutant. The body generates antioxidants to detoxify harmful particles and limit the corresponding allergic reaction.

Researchers sampled the DNA of volunteers who are allergic to ragweed to find which forms of the genes they had. The participants were then given doses of ragweed through the nose, followed by either a placebo or quantities of diesel exhaust particles equivalent to breathing the air in Los Angeles, CA, for 40 hours.

The mix of ragweed and diesel exhaust triggered greater allergic responses than ragweed alone. Additionally, the diesel particles caused volunteers who lacked the antioxidant-producing form of the GSTM1 gene to have significantly greater allergic responses, compared to the other participants.

Up to 50 percent of the U.S. population does not have this form of the GSTM1 gene. Within the group that lacked GSTM1, those who had a particular variant of the GSTP1 gene experienced even greater allergic reactions. Researchers estimate that 15 to 20 percent of the U.S. population falls into this category.

'Diesel emissions can trigger allergic symptoms, but the genetic factors involved in the process are quite complex,' says David Diaz-Sanchez, Ph.D., assistant professor in the Division of Immunology and Allergy at the University of California Los Angeles, who co-authored the study with scientists from the University of Southern California.

'Our findings suggest that people who lack the genes to make key antioxidants may have difficulty fighting the harmful effects of air pollution.'

Dr. Diaz-Sanchez says that he and the other researchers will work to find other genes involved in pollution-related health problems such as asthma, lung cancer and heart disease, with the goal of discovering possible treatments and preventions.

'We are focused on investigating ways we can overcome this genetic deficiency,' he says. 'This may be accomplished by either giving people drugs that replace the role of the genes or by boosting the body's natural defenses.'

NIAID is a component of the National Institutes of Health (NIH), which is an agency of the Department of Health and Human Services. NIAID supports basic and applied research to prevent, diagnose and treat infectious and immune-mediated illnesses, including HIV/AIDS and other sexually transmitted diseases, illness from potential agents of bioterrorism, tuberculosis, malaria, autoimmune disorders, asthma and allergies.

Reference: F Gilliland et al. Effect of glutathione-S-transferase M1 and P1 genotypes on xenobiotic enhancement of allergic responses: randomised, placebo-controlled crossover study. The Lancet 363 (9403): 119-25 (2004).

Press releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at http://www.niaid.nih.gov.