title: Genetic aspects of susceptibility to air pollution.
abstract: Inter-individual variation in human responses to air pollutants suggests that some subpopulations are at increased risk, and it is increasingly clear that genetic background is an important susceptibility factor. Genetically standardised animal models provide useful investigative tools. Linkage analyses using inbred mice identified chromosomal segments (quantitative trait loci (QTL)), with genes controlling susceptibility to the lung inflammatory (chromosome 17), injury (chromosome 11), and hyperpermeability (chromosome 4) responses to ozone (O3) exposure. An immune dysfunction response induced by exposure to sulphate-associated particles is linked to the identical chromosome 17 and 11 QTLs described for O3 susceptibility, thus similar genetic mechanisms may be controlling pulmonary responses to these pollutants. Candidate genes within the QTLs on chromosomes 4 and 17 include the toll-like receptor 4 and the pro-inflammatory cytokine, tumour necrosis factor-alpha, respectively. Functional analyses strongly support a role for these candidate genes in determining susceptibility to O3 and particulates. Because striking linkage homology exists between the human and mouse genomes, candidate susceptibility genes identified in the mouse are likely to aid research aimed at understanding human genetic factors that contribute to differential susceptibility. To date, no studies have examined the interaction between age and genetic background in the development of air pollution-induced lung disease. However, investigations have suggested an influence of age on genetic susceptibility to lung cancer and other diseases, which indicate that an interaction between age and genetic background may be important in air pollution disease pathogenesis.
authors.affiliation: Dept of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA. kleeber1@niehs.nih.gov
authors.forename: S R
authors.initials: SR
authors.lastname: Kleeberger
mesh_terms: D000367:Age Factors; D000368:Aged; D000393:Air Pollutants / Q000009:adverse effects*; D000397:Air Pollution / Q000009:adverse effects*; D000818:Animals; D002874:Chromosome Mapping; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006801:Humans; D008171:Lung Diseases / Q000209:etiology / Q000235:genetics*; D010126:Ozone / Q000009:adverse effects
chemical_list: D000393:Air Pollutants; D010126:Ozone