Itch, sneeze and wheeze: the genetics of atopic allergy

Abstract

In many developed countries over one-fifth of the population are affected by one or more atopic allergic disorders. Several time-trend studies indicate that the prevalence and severity of eczema, rhinitis, and asthma is rapidly increasing1,2,3; and this observation, coupled with the widespread geographical variations in disease prevalence noted by the International Studies of Asthma and Allergies in Childhood, points to the strong contribution of environment to the aetiology4. However, the tendency of atopic allergic conditions to cluster both within individuals and within families suggests that genetic factors are also important. Asthma is a condition characterized by reversible airflow obstruction and lower airway hyper-responsiveness, which results in episodic cough, wheeze and shortness of breath5. Inflammation of the nasal passages, manifesting as sneezing, nasal blockage and itchy rhinorrhoea, is the symptom complex known as rhinitis6. Eczema is the commonest cause of dermatitis in developed countries and affects approximately 20% of the general population7. The distribution of eczematous lesions varies with age, the face and trunk being most affected in infants whereas the flexor aspects of the limbs are typically affected in older children and adults. Advances in our understanding of the immunobiology of these disorders have shown them to have a common pathophysiological basis—an exaggerated and inappropriate IgE-mediated inflammation in response to allergen exposure—referred to as atopy8. The absence of objective and reliable criteria for defining either atopy or the atopic allergic conditions (eczema, rhinitis and asthma) has been and continues to be a major obstacle to establishing the genetic basis of atopic disorders. This review is based in the main on articles retrieved by searching Medline, EMBASE and OMIM (Online Mendelian Inheritance in Man) electronic databases. Key websites of possible relevance were also searched9, including those of the British Society for Human Genetics10, the European Society for Human Genetics11, and the Human Mutation Database12. Allergy and genetic texts were consulted, and the analysis was helped by personal contacts with several experts on human genetics.