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Genetic make up and environmental factors in the pathogenesis of allergic disorders
  1. A Khan
  1. Specialist Registrar in Respiratory Medicine, Derriford Hospital, Plymouth, UK;

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It is well known that air pollution increases morbidity from asthma and other allergic disorders. The genetic factors that underlie this process are complex and poorly understood. Oxidative stress has emerged as an important mechanism in the toxic effects of environmental pollution. The ability of an individual to neutralise these reactive oxygen species seems to be important in modifying allergic responses. Members of the enzyme glutathione S-transferase superfamily (GSTM1, GSTT1, and GSTP1) provide the major defence system against oxidative stress.

Gilliland and colleagues conducted a randomised, placebo controlled, crossover study to test the hypothesis that null genotypes for GSTM1, GSTT1, and GSTP1 codon 105 variants are the key genotypes that combat the oxidative stress. Nineteen atopic volunteers were included in the study. They had intranasal challenges with either allergen plus placebo or allergen plus diesel exhaust particles. The allergic response was observed by measuring surrogate markers of allergic response (IgE, histamine, interleukin-4, interferon-γ). Genotypes were identified in all the participants. The results showed that the participants with null GSTM1 or GSTP1 wild type had an enhanced nasal allergic response to diesel exhaust particles with a statistically significant rise in surrogate markers. This suggests that polymorphism in genotypes affects the defensive response against oxidative stress.

This important study suggests a direct way in which pollution could be triggering an allergic response. This susceptibility seems to be regulated by genetic factors and hence opens up the possibility of new therapeutic interventions.

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