Reviews and feature articleGene-environment interactions in asthma
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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Series editors: Donald Y. M. Leung, MD, PhD, and Dennis K. Ledford, MD