Genetics of allergic disease

The understanding that genetics play a role in allergic disease and asthma has been recognized for more than 100 years. This genetic component was suggested through observations that allergic subjects had a significantly higher incidence of family histories of disease as compared with controls [1,2]. Follow-up studies have shown that if one parent has allergies, a child has a 33% chance of developing allergies and if both parents are allergic that number jumps to a 70% chance. The link to asthma is not quite as strong, because a child only has a 15% chance of developing asthma if one parent has the disease. A dominant or recessive model of inheritance for atopy or asthma has not been supported in association studies, which led to a period of time where the idea of inheritance of atopy was in question. Eventually, it was recognized that allergies and asthma represent complex genetic disorders, defined as disorders that have numerous contributing genes, each having variable degrees of involvement in any given individual. In addition to specific genes, environmental exposures (including allergen exposure, secondhand cigarette smoke, pollutants), low birth weight, infectious agents, and numerous other factors have been recognized to contribute to the development of allergies and asthma through their ability to influence gene expression. The results of twin studies suggest that approximately 50% of the risk for developing asthma is related to genetic factors with an equivalent risk associated with environment [3]. This article covers three areas involved in the genetics of allergic disease: (1) the association studies performed in allergy and asthma, (2) functional genomics of candidate genes, and (3) pharmacogenetics.