Program for Population Genetics, Harvard School of Public Health, Boston, Massachusetts, USA.
BMC Med Genet. 2009 Dec 1;10:123. doi: 10.1186/1471-2350-10-123.
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.
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. Both single SNP and haplotype analyses were performed.
We found that DPP10 was significantly associated with bronchial hyperresponsiveness (BHR) and BHR asthma after the adjustment for multiple testing; while the associations of PHF11 with positive skin reactions to antigens and the associations of HLA-G with BHR asthma were only nominally significant.
Our study is the first one to provide additional evidence that supports the roles of DPP10 in influencing asthma or BHR in a Chinese population.
在报道的连锁研究之后，已经定位克隆了位于不同染色体区域的六个哮喘候选基因，ADAM33、NPSR1、PHF11、DPP10、HLA-G 和 CYFIP2。对于 ADAM33、NPSR1 和 CYFIP2，已经在东亚人群（如中国和日本）中研究了与哮喘或哮喘相关表型的关联。然而，对于 PHF11、DPP10 和 HLA-G，在亚洲人群中尚未进行任何关联研究。因此，本研究旨在检测这三个定位克隆基因与中国人群中哮喘或哮喘相关表型的关联。
在鉴定的 PHF11、DPP10 和 HLA-G 的顶部区域中，分别检测了两个、五个和两个单核苷酸多态性（SNP）。研究样本是根据哮喘发病情况和至少以下三个哮喘相关表型之一的极值选择的：总血清免疫球蛋白 E 水平、支气管反应性测试和皮肤点刺测试。进行了单 SNP 和单倍型分析。
我们发现 DPP10 与支气管高反应性（BHR）和 BHR 哮喘显著相关，在经过多重检验调整后；而 PHF11 与抗原阳性皮肤反应的关联以及 HLA-G 与 BHR 哮喘的关联仅具有名义显著性。
我们的研究首次提供了额外的证据，支持 DPP10 在影响中国人群中的哮喘或 BHR 中的作用。
