Replication of Associations between Three Positionally Cloned Asthma Candidate Genes and Asthma or Asthma-related Phenotypes in A Chinese Population

Background: Six asthma candidate genes, ADAM33, NPSR1, PHF11, DPP10, HLA-G, and CYFIP2, located at different chromosome regions have been positionally cloned following the reported linkage studies. For ADAM33, NPSR1, and CYFIP2, the associations with asthma or asthma-related phenotypes have been studied in East Asian populations such as Chinese and Japanese. However, for PHF11, DPP10, and HLA-G, none of the association studies have been conducted in Asian populations. Therefore, the aim of the present study is to test the associations between these three positionally cloned genes and asthma or asthma-related phenotypes in a Chinese population. Methods: Two, five, and two single nucleotide polymorphisms (SNPs) in the identified top regions of PHF11, DPP10, and HLA-G, respectively, were genotyped in 1183 independent samples. The study samples were selected based on asthma affectation status and extreme values in at least one of the following three asthma-related phenotypes: total serum immunoglobulin E levels, bronchial responsiveness test, and skin prick test. Results: Single SNP and haplotype analyses revealed that PHF11 was associated with positive skin reactions to antigens; DPP10 was associated with bronchial hyperresponsiveness (BHR) and BHR asthma; and HLA-G was associated with BHR asthma. Conclusions: Our study is the first one to support the roles of PHF11, DPP10, and HLA-G in influencing asthma and asthma-related phenotypes, such as skin prick test and BHR, in a Chinese population.