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Gene-environment interactions in asthma

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Asthma is a complex disease, and its incidence is determined by an intricate interplay of genetic and environmental factors. The identification of novel genes for asthma suggests that many genes with small effects rather than few genes with strong effects contribute to the development of asthma. These genetic effects may in part differ with respect to a subject's environmental exposures, although some genes may also exert their effect independently of the environment. Whereas the geneticist uses highly advanced, rapid, comprehensive technologies to assess even subtle changes in the human genome, the researcher interested in environmental exposures is often confronted with crude information obtained from questionnaires or interviews. There is thus substantial need to develop better tools for individual exposure assessment in all relevant environmental fields. Despite these limitations, a number of important gene-environment interactions have been identified. These interactions point to the biology of environmental exposures as the involved genetic variation is suggestive of certain underlying mechanisms. Furthermore, the identification of subjects who are particularly susceptible to environmental hazards through genetic analyses helps to estimate better the strength of effect of environmental exposures. Finally, the analysis of gene-environment interactions may result in a reconciliation of seemingly contradictory findings from studies not taking environmental exposures into account.

Section snippets

Asthma is a disease of the airways in the lung

The cardinal symptom of asthma is reversible wheeze over time or by medication, hinting at a variable airway abnormality as an underlying phenomenon. In acute episodes, the airway obstruction is audible through a stethoscope, or in more severe attacks, by the patient and physician without an auxiliary tool. The airway obstruction is furthermore indirectly visible on outputs of various measures of lung function testing. Beyond these instruments, we have very few means of imaging the affected

Asthma might be not one disease but many

Although we cannot rule out with certainty that 1 or a few unidentified causes underlie the development of asthma at all ages and varying clinical manifestations, there is evidence to suggest that many pathways open out into 1 rather uniform clinical presentation. From other areas of medicine, this is a well known fact. For example, anemic patients often present with pallor and fatigue as the only symptoms, yet a large variety of differential diagnoses is guiding the work-up of such a patient.

Genetics of asthma

With the introduction of new powerful genetic tools, the heritable component of asthma has gained increasing attention over the last few years. With these extraordinary technological advances, the identification of alterations in the sequence of the base pairs of our DNA may help us understand better the underlying biology of asthma and lead to the discovery of so far unknown processes in the airways resulting in the development of the disease. This expectation calls for open approaches to the

Gene by environment interactions in asthma

Gene-by-environment interactions have been defined as a situation “when, because of their genetic differences, two or more individuals, families or genotypic lines respond differently, or to different extents, to change in the environment.” (p 387)20 Most of the performed studies on gene-environment interactions are based on this principle. In contrast with population-based studies in which the average effect of an environmental exposure is compared between groups, the identification of

Pharmacogenetics

There are several categories of medications for the treatment of asthma. However, not all patients with asthma have the same response to these medications. Because interindividual responses to asthma medications can vary considerably, the potential for genetic contributions to variable drug responses to β-agonists, anticholinergics, leukotriene modifiers, and corticosteroids may be significant. The rapidly evolving field of pharmacogenetics, which aims at establishing a more personalized

Conclusion

Asthma is a complex disease, and its incidence is determined by an intricate interplay of genetic and environmental factors. Asthma is likely a syndrome rather than 1 disease entity, in which different pathways eventually result in various phenotypes of variable airway obstruction. The identification of novel genes for asthma suggests that many genes with small effects rather than a few genes with strong effects contribute to the development of asthma. These genetic effects may in part differ

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