Environmental risk factors • Allergen exposure • Exposure to indoor and outdoor air pollution • Bacterial/viral infection • Others Induce/enhance symptoms and allergic sensitization Allergic diseases • Allergic rhinitis • Asthma • Eczema Specific immunologic mechanism • IgE- / non IgE-mediated Differences in lifestyle • Early life features • Nutrient intake • Family and sibship size • Hygiene standard • Food • Vaccination • Stress • Ownership of pets • Others Figure 1 Risk factors of allergic diseases. frequency is less frequent in Caucasians than Asian populations with a difference of up to 6-fold. The T allele is common (70%–73%) in Japanese (Noguchi et al 1998b), but less common (12.5%) in Germans (Kabesch et al 2003). Our recent study showed a significant difference of T allele frequency at IL-4/-590 among Chinese (non-atopic 90.2% and atopic 87.3%), Malays (non-atopic 83.3% and atopic 77.1%), and Asian Indians (non-atopic 38.1% and atopic 44.1%) (Unpublished data). For the IL-4R, the association of atopy with a gain-of-function mutation in the α subunit of the IL-4 receptor (Q576R) was found to be a critical condition of atopy (Hershey et al 1997). On the contrary, a study performed in Singapore has reported a significant ethnic variation of this polymorphism among Chinese, Malays, and Indians, and no association was found between this polymorphism and atopy in all three ethnic groups (Tan et al 1999). To date, neither fine mapping nor particular genetic polymorphisms have been confirmed to be a critical condition in the development or clinical manifestations of allergic diseases. It is not surprising since predisposition to atopy is influenced by a complex immune procedure, including interactions of multiple genes, interaction of Therapeutics and Clinical Risk Management 2005:1(2) Allergic rhinitis Genetic disposition genetic polymorphisms or haplotypes Chromosomes 1, 2, 3, 5, 6, 7, 9, 11, 12, 13, 14, 16, 17, 19, etc • Specific immune response • Imbalance of Th1 and Th2 cells and cytokine production • IgE production • Response or functions of the IgE receptors • Recruitment and activation of inflammatory cells and airway inflammation • Others mechanisms environmental and genetic factors, and population heterogeneity. Future studies are needed to identify the key genes or the joint effect of several susceptibility genes (haplotypes) that leads to allergic phenotypes. Furthermore, statistical methods for discovering sets of susceptible genes and environmental factors, as well as systematic verifications of the gene-environment-disease network would have a great impact on future genetic epidemiological studies (Hoh and Ott 2004). Environmental factors Environmental factors such as increased air pollution, changed lifestyle, and decrease in bacterial/viral infection are frequently quoted as adjuvant factors for allergic sensitization and possible causes of the increased prevalence. Protective effect of infections on atopy – “hygiene hypothesis” During the past decade, the simulative question of why atopic diseases are increasing in prevalence, which is inversely proportional to the prevalence of communicable diseases, is due to the improvement of healthcare policy 117