Gene-Environment Interactions Trigger Increased Allergic Response

NEW YORK (Reuters Health) - Common variants in genes encoding glutathione-S-transferases (GSTs) increase allergen responsiveness in sensitive patients exposed to diesel exhaust, investigators in California report in the January 10th issue of the Lancet.

While these findings explain why some individuals are more susceptible to the effects of air pollution, they also suggest that antioxidants - such as vitamins A, E and C and other antioxidant agents under investigation - could prevent the potentiating effect of air pollution on allergic inflammation, lead investigator Dr. Frank D. Gilliland told Reuters Health.

GSTs metabolize reactive oxygen species and detoxify chemicals present in diesel exhaust, and GSTP1 and GSTM1 polymorphisms are associated with airway hyperresponsiveness and asthma. Dr. Gilliland, at the University of Southern California in Los Angeles, and his team estimate that 15% to 20% of the general population carries both the GSTM1 null genotype and the I/I variant of GSTP1 gene.

To investigate the mechanism driving the effects of air pollution on allergic responses, Dr. Gilliland's group evaluated genotypes in 19 patients with ragweed sensitivity and a history of allergic rhinitis.

Subjects were challenged intranasally on two occasions, once with allergen plus saline and one time with allergen plus 0.3 mg diesel exhaust particles in saline (the equivalent of 40 hours of exposure to air in Los Angeles). Histamine response was measured in nasal lavage fluid 10 minutes post-challenge and IgE, interleukin 4 and interferon gamma responses were assessed 24 hours later.

The 14 subjects with a null GSTM1 and the 13 homozygous GSTP1 I genotype exhibited significantly higher nasal IgE and histamine responses to diesel exhaust particles than to the allergen alone. And in the 11 participants with both susceptibility variants, "diesel exhaust had a huge adjuvant effect on the allergic response to allergens," increasing response up to 20 times greater than allergen exposure alone, Dr. Gilliland said.

In the past, lacking GSTM1 or GSTP1 activity normally would not have made much difference to human health, he explained. "But now that we have new and increasing levels of pollutants, that's at least partially what is bringing on some of the increases in allergy susceptibility."

He noted that in some populations, 50% to 60% of individuals have allergies, "and that's very different from what it was 50 or 100 years ago."

"We now have ways to identify individuals susceptible to air pollution, and, because this sensitivity seems to be regulated by genetic and dietary factors, new approaches are emerging that might help protect these individuals from ambient pollution," Drs. F. J. Kelly and Thomas Sandstrom remark in a related commentary. Dr. Kelly is on staff at King's College in London, and Dr. Sandstrom is at University Hospital, Umea, Sweden.

Source: Lancet 2004;363:95-96,119-125. [ Google search on this article ]

MeSH Headings: Diagnosis : Diagnostic Techniques, Respiratory System : Nasal Provocation Tests : Diagnostic Techniques and Procedures : Analytical, Diagnostic and Therapeutic Techniques and Equipment