Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio, United States of America.
PLoS One. 2011 Feb 28;6(2):e16522. doi: 10.1371/journal.pone.0016522.
Candidate gene case-control studies have identified several single nucleotide polymorphisms (SNPs) that are associated with asthma susceptibility. Most of these studies have been restricted to evaluations of specific SNPs within a single gene and within populations from European ancestry. Recently, there is increasing interest in understanding racial differences in genetic risk associated with childhood asthma. Our aim was to compare association patterns of asthma candidate genes between children of European and African ancestry.
METHODOLOGY/PRINCIPAL FINDINGS: Using a custom-designed Illumina SNP array, we genotyped 1,485 children within the Greater Cincinnati Pediatric Clinic Repository and Cincinnati Genomic Control Cohort for 259 SNPs in 28 genes and evaluated their associations with asthma. We identified 14 SNPs located in 6 genes that were significantly associated (p-values <0.05) with childhood asthma in African Americans. Among Caucasians, 13 SNPs in 5 genes were associated with childhood asthma. Two SNPs in IL4 were associated with asthma in both races (p-values <0.05). Gene-gene interaction studies identified race specific sets of genes that best discriminate between asthmatic children and non-allergic controls.
CONCLUSIONS/SIGNIFICANCE: We identified IL4 as having a role in asthma susceptibility in both African American and Caucasian children. However, while IL4 SNPs were associated with asthma in asthmatic children with European and African ancestry, the relative contributions of the most replicated asthma-associated SNPs varied by ancestry. These data provides valuable insights into the pathways that may predispose to asthma in individuals with European vs. African ancestry.
候选基因病例对照研究已经确定了几个与哮喘易感性相关的单核苷酸多态性（SNP）。这些研究大多数都局限于评估单一基因内的特定 SNP 以及欧洲血统人群中的 SNP。最近，人们越来越关注理解与儿童哮喘相关的遗传风险的种族差异。我们的目的是比较欧洲和非洲裔儿童哮喘候选基因的关联模式。
方法/主要发现：使用定制的 Illumina SNP 芯片，我们对辛辛那提儿科诊所资料库和辛辛那提基因组控制队列中的 1485 名儿童进行了基因分型，对 28 个基因中的 259 个 SNP 进行了评估，并评估了它们与哮喘的关联。我们确定了 14 个位于 6 个基因中的 SNP，这些 SNP 与非裔美国人的儿童哮喘显著相关（p 值<0.05）。在白种人中，5 个基因中的 13 个 SNP 与儿童哮喘相关。IL4 中的两个 SNP 与两种种族的哮喘相关（p 值<0.05）。基因-基因相互作用研究确定了最佳区分哮喘儿童和非过敏性对照的种族特异性基因集。
结论/意义：我们确定 IL4 在非裔美国人和白种儿童的哮喘易感性中起作用。然而，虽然 IL4 SNP 与具有欧洲和非洲血统的哮喘儿童的哮喘相关，但最常被复制的与哮喘相关的 SNP 的相对贡献因血统而异。这些数据为个体的欧洲与非洲血统可能导致哮喘的途径提供了有价值的见解。
