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Genetic aspects of susceptibility to air pollution

Dept of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA

CORRESPONDENCE: S.R. Kleeberger, Laboratory of Pulmonary Pathobiology, National Institute of Environmental Health Sciences, National Institutes of Health, 111 T.W. Alexander Dr, Building 101, Rm. D240, Research Triangle Park, NC 27709, USA. Fax: 1 9195414133. E-mail: kleeber1@niehs.nih.gov

Keywords: innate immunity, ozone, particles, polymorphism, toll-like receptor 4, tumour necrosis factor-

Received: April 12, 2002
The author was supported by grants from the National Institutes of Health (HL57142, ES09606, and P30 ES00002) and the Environmental Protection Agency (R826724).

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-, 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.