Gene by environment interactions and the development of asthma and allergy

Asthma is the most common chronic disease during childhood in modern societies. Prevalence rates differ between countries, but on an average, 10-20% of the children in Western Europe and the US are affected. While the true cause of the disease is not yet known, it is common perception that genetic alterations and environmental factors act together in the development of atopic diseases such as asthma, allergic rhinitis and atopic eczema. Numerous studies have reported an association between environmental tobacco smoke (ETS) exposure and respiratory diseases: maternal smoking during pregnancy and early childhood is associated with impaired lung growth and diminished lung function, and in asthmatic children parental smoking increases symptoms and the frequency of asthma attacks. Recent studies have shown that the capability of ETS to induce asthma and asthma symptoms may be modified by genetics. Linkage studies, which took smoking and passive smoking status of study subjects into account, came to different results than those studies based on unstratified samples. These analyses indicated that some chromosomal regions (e.g. 5q) might harbor genes that exert their effects predominantly in combination with ETS exposure. Some of the genes modifying the effect of ETS and air pollution on the body may have been identified. When these detoxification enzymes are genetically defect or missing the capability of the lung to metabolize hazardous substances is dramatically diminished. As a consequence, pulmonary inflammation may occur and the barrier function of the lung may be compromised allowing allergens to penetrate and asthma to start. Knowledge of these interactions may be the key in understanding the complex nature of the disease. It may allow for prediction and an earlier diagnosis of the disease as well as better and more efficient prevention. In the long run, it may contribute significantly to the development of new and better-tailored drugs for one of the major diseases of the 21st century.