Gene-Air Pollution Interactions in Asthma

Abstract

Genetic and environmental factors interact to cause asthma. However, genetic studies have generally ignored environmental factors and environmental studies have generally ignored genetics. Thus, there are few examples from the literature of specific geneenvironment interactions in relation to asthma. The clearest examples of genetic interactions for inhaled pollutants exist for endotoxin, environmental tobacco smoke, and ozone. Endotoxin -genetic interactions in asthma are the focus of two other manuscripts from this conference, so this review focuses on environmental tobacco smoke and ozone. In the sparse literature, there is evidence for the role of specific genes involved in oxidative stress, notably GSTM1 and TNF, in the respiratory responses to ozone and environmental tobacco smoke. There are few data on genes involved in innate immune pathways, which are crucial in response to endotoxin and may play a role in response to ozone and environmental tobacco smoke. Genes involved in oxidative stress may interact with both air pollutants and diet in relation to asthma phenotypes. Future directions to advance the field include whole genome association studies, better assessment of exposure and phenotypes, and consideration of joint interactions with diet and other co-factors that influence individual susceptibility.

Early-Life Air Pollution and Asthma Risk in Minority Children. The GALA II and SAGE II Studies

“…ROS can oxidize nearby macromolecules, resulting in cellular damage or "oxidative stress," which is thought to modify the pulmonary inflammatory response (44). There is also evidence that underlying genetic traits may alter the susceptibility to asthma in the presence of air pollution (45). Many of the previously identified gene variants are related to immune cell responses (46) and prevention of oxidative damage from ROS (47).…”

Air Pollution and Lung Function in Minority Youth with Asthma in the GALA II (Genes–Environments and Admixture in Latino Americans) and SAGE II (Study of African Americans, Asthma, Genes, and Environments) Studies

“…Furthermore, alleles protective for the risk of asthma have been found to be more common in Native American populations, and, among Latinos, have been found in greater frequency among Mexican populations compared with other Latinos (23)(24)(25). Specific gene variants have also been linked to increased susceptibility of asthma in the presence of air pollution (26)(27)(28). These findings suggest the possibility of population-specific responses to ambient air pollution and possible modification of air pollution effects by genetic ancestry.…”

Occupational exposure to dust, gases and fumes, a family history of asthma and impaired respiratory health

“…It is well known that there are susceptibility factors for impaired respiratory health (eg, persons with a family history of asthma or atopy have an increased risk) (11). However, whether health effects of occupational exposure to air pollutants differ among persons with and those without susceptibility factors has been less studied (11). In this longitudinal populationbased study, we estimated the impact of occupational exposure on respiratory health in a general, adult, occupationally active population with respect to a family history of asthma.…”