Asthma severity and genetics in Taiwan

Abstract

The prevalence of childhood asthma in Taiwan has increased dramatically during the last 2 to 3 decades. In Taipei city, the prevalence of asthma in schoolchildren has increased from 1.3% in 1974 to 19.0% in 2003. Genetic mapping and candidate gene analyses have revealed suggestive evidence for linkage of asthma to a number of different chromosomal regions and for association with several candidate genes. Over 70 variants in candidate genes have been reported to be associated with these phenotypes. The main regions these variants have been found are on chromosomes 2q, 5q, 6p, 11q, 12q, 16q and 17q. Five potential asthma susceptibility genes or complexes have been identified using a positional approach. These are A desintegrin and metalloproteinase 33 (ADAM33), dipeptidyl peptidase 10 (DPP10), plant homeodomain zinc finger protein 11 (PHF11) and SET domain, bifurcated 2, G-protein related receptor for asthma (GPRA) and serine protease inhibitor Kazal type 5 (SPINK5). It is also evident that environmental factors will influence the expression of genes and the ultimate clinical phenotype of asthma and atopy. Evidence for a genetic contribution to risk for fatal or near-fatal asthma in Caucasians and Taiwanese has been suggested. We have revealed that the regulation upon activation, normal T cell expressed and secreted (RANTES)-28C/G polymorphism exacerbates asthma severity and represents a genetic risk factor for life-threatening asthma attacks in Chinese children. Moreover, in the Chinese children the frequency of the chemoattractant receptor-homologous molecule expressed on T helper 2 cells (CRTH2) 1651G allele in near-fatal asthmatics was significantly higher than in mild-to-moderate asthmatics and normal controls. The CRTH2 1651G allele of single nucleotide polymorphism re545659 was also associated with a higher degree of bronchial hyperresponsiveness.