REVIEW

Genetic susceptibility to the respiratory effects of air pollution

I A Yang^1,2, K M Fong^1,2, P V Zimmerman^1,2, S T Holgate³ and J W Holloway^3,4

¹ School of Medicine, The University of Queensland, The Prince Charles Hospital, Brisbane, Australia
² Department of Thoracic Medicine, The Prince Charles Hospital, Brisbane, Australia
³ Infection, Inflammation and Repair Division, University of Southampton, Southampton, UK
⁴ Human Genetics Division School of Medicine, University of Southampton, Southampton, UK

Correspondence to:
Dr I Yang, Department of Thoracic Medicine, The Prince Charles Hospital, Rode Road, Chermside, Brisbane QLD 4032, Australia; Ian_Yang{at}health.qld.gov.au

There is large variation between individuals in their response to air pollutants. This review summarises the existing evidence that genetic factors influence the mechanisms of lung injury caused by air pollutants. Genetic association studies have compared the adverse effects of air pollutants between subjects with specific genotypes in biologically relevant genes. In human studies of ozone exposure, polymorphisms in oxidative stress genes (NQO1, GSTM1, GSTP1) modify respiratory symptoms, lung function, biomarkers and risk of asthma. Inflammatory gene polymorphisms (TNF) influence the lung function response to ozone, and the effect of different levels of ozone on the development of asthma. Polymorphisms in oxidative stress genes (GSTM1, GSTP1) alter the response to combined exposure to ragweed pollen and diesel exhaust particles. Importantly, polymorphisms in an oxidative stress gene (GSTM1) have predicted patients with asthma who benefit from antioxidant supplementation in Mexico City, which has chronically high ozone exposure. Genetic linkage studies of families have not been feasible for studying the effects of air pollution in humans, but some progress has been made with pedigrees of specially bred mice, in identifying chromosomal regions linked to effects of ozone or particles. A high priority now, in addition to avoiding exposure in the most susceptible people, is to clearly identify the most effective and safe chemopreventive agents for individuals who are genetically susceptible to the adverse effects of air pollution (eg, antioxidants to be taken during high ozone levels).

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