Genetic mechanisms of susceptibility to ozone-induced lung disease

Environmental oxidants remain a major public health concern in industrialized cities throughout the world. Population and epidemiological studies have associated oxidant air pollutants with morbidity and mortality outcomes, and underscore the important detrimental effects of these pollutants on the lung. Interindividual variation in pulmonary responses to air pollutants suggests that some subpopulations are at increased risk to detrimental effects of pollutant exposure, and it has become clear that genetic background is an important susceptibility factor. A number of genetics and genomics tools have recently emerged to enable identification of genes that contribute to differential responsiveness to oxidants, including ozone (O(3)). Integrative omics approaches have been applied in inbred mice to identify genes that determine differential responsiveness to O(3)-induced injury and inflammation, including Tnf, Tlr4, and MHC Class II genes. Combined investigations across cell models, inbred mice, and humans have provided, and will continue to provide, important insight to understanding genetic factors that contribute to differential susceptibility to oxidants.