In groundbreaking research using laboratory animals, researchers at the schools of Public Health and Medicine have found that genetic background is an important risk factor in how susceptible a person will be to the toxic effects of particulate air pollution. According to the researchers, genetic risk factors may help explain the increasing incidence of pollution-related disease and mortality in urban areas. The researchers located two quantitative trait loci that control susceptibility to toxic effects of particle exposure. The study was published in the May issue of the American Journal of Respiratory Cell and Molecular Biology.
Human exposure to particulate air pollution has been linked to decreases in lung function and increases in respiratory illness, such as chronic cough, bronchitis and pneumonia, but the precise toxicological or physiological reasons for this link have not been elucidated. Although some subpopulations--children, the elderly and patients with pre-existing chronic diseases--seem to be particularly at risk, scientists believe that not all particle-associated morbidity and mortality can be attributed solely to age or pre-existing disease.
According to senior author Steven R. Kleeberger, associate professor in the Department of Environmental Health Sciences, School of Public Health, "Identification of these susceptibility genes will lead to a better understanding of the effects of air pollution on respiratory health. Individuals with a genetic predisposition to an impaired immune response may be more susceptible to pollution-associated viral and bacterial respiratory infections that lead to hospitalization. Gene characterization may thus provide a means for identifying susceptible individuals and developing drug strategies to prevent lung injury."
The investigators used inbred mice, which are standardized genetically, as models since the mouse and human genome have important similarities. The mice were exposed to acid-coated particles at high humidity for four hours. These particles, produced by the co-generation of carbon black aerosol and sulfur dioxide, mimic one component of the airborne acid aerosols found in high concentrations in many large urban areas in the eastern United States. Control groups were exposed to filtered air only.
As the foundation for this research, the scientists had demonstrated that susceptibility to pollution was genetically based and that this susceptibility was probably inherited as a recessive trait. In this study, they surveyed the entire genome of the mouse in search of correlations between the immune response and genetic markers, and used advanced gene-mapping techniques to identify the chromosomal regions in question.
The researchers discovered regions on chromosomes 17 and 11 that accounted for much of the genetic variance in susceptibility to the acid-coated particles. Fine-mapping studies are under way to narrow the length of the two chromosomal regions, which will lead to precise identification of the susceptibility genes.
The study was supported by the Johns Hopkins NIEHS Center and a grant from the Environmental Protection Agency.