Association of IL4R gene polymorphisms with asthma in Chinese populations.

Cytokines, having central functions in immunological and inflammatory processes, are expected to play important roles in the pathogenesis of various diseases, such as asthma. Genetic polymorphisms of those cytokine and cytokine receptor genes are the focus of genetic association studies. In an effort to identify gene(s) whose variant(s) are associated with asthma, we screened all exons and their flanking regions, as well as the promoter region (1.5kb) of eight genes, including IL4, IL13, IL12B, IL5, IL3, IL9, CD14 and IL4R. We identified 42 single nucleotide polymorphisms, 15 of which were novel. Then, we examined the genetic effects of 30 single nucleotide polymorphisms in eight cytokine and cytokine receptor genes on asthma in a Chinese asthma cohort (n = 537). Genetic association analysis of polymorphisms revealed that six polymorphisms (c.899-2C>A, c.1199A>C, c.1242G>T, c.1291T>C, c.1299T>C, c.1507T>C) in the IL4R gene, three of which resulted in an amino-acid change, showed significant association with the risk of asthma (P = 0.00023). Further analysis indicates that these six polymorphisms segregated in strong linkage disequilibrium. The genetic association of IL4R with asthma might provide valuable insights into the pathogenesis of asthma.