Asthma, genes, and air pollution

Objective: The objective of this article is to evaluate genetic risks associated with the pulmonary response to air pollutants, including particulates and ozone. Methods: A comprehensive review of articles related to the genetics of asthma with particular attention to air pollution was conducted through a search of the National Library of Medicine's PubMed database. Results: Asthma, which affects over 15 million people in the United States, is characterized by inflammation leading to reversible airflow obstruction. Triggered by exposure to numerous occupational and environmental agents, asthma has long been considered to occur more frequently in families, with upwards of a 50% higher rate in the offspring of parents with asthma. Asthma genetic studies have used two major methods: mapping techniques that pinpoint gene loci and studies that identify genes and polymorphisms associated with various asthma mechanisms such as inflammatory mediators. The most consistently replicated chromosomal regions associated with asthma have been chromosomes 2q, 5q, 6p, 12q, and 13q. Because the formation of reactive oxygen species is a major aspect of the inflammatory process of asthma, genetic aberrations associated with antioxidants such as glutathione S-transferase (GST) may shed light on reasons why some people with asthma seem more at risk of exacerbations as a result of air pollution. People with a polymorphism at the GSTP I locus, which codes for GST, one of a family of pulmonary antioxidants, have higher rates of asthma. Children in Mexico City with the GSTM1 null genotype demonstrated significant ozone-related decrements in lung Junction. Animal studies support the key role of antioxidants in reducing the inflammatary response associated with exposure to diesel exhaust particles. Conclusions: Oxidative stress is a key mechanism underlying the toxic effects of exposure to some types of air pollution. Asthmatics with the null genotype for the antioxidant, GST, seem more at risk of the pulmonary effects of air pollution.