Cosmopolitan and ethnic-specific replication of genetic risk factors for asthma in 2 Latino populations
Cosmopolitan and ethnic-specific replication of genetic risk factors for asthma in 2 Latino populations
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DOI：
10.1016/j.jaci.2011.03.050
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发表时间：
2011-07-01
影响因子：
14.2
通讯作者：
Burchard, Esteban G.
中科院分区：
文献类型：
--
作者：
Galanter, Joshua M.;Torgerson, Dara;Burchard, Esteban G.
背景：尽管墨西哥人和波多黎各人被共同归类为“西班牙裔/拉丁裔”，但两组之间在哮喘患病率、严重程度和死亡率方面存在显著差异。我们试图检查特定人群的遗传风险导致这种差异的可能性。目的：超过100个候选基因与哮喘相关，并在独立人群中进行了复制，并进行了7项哮喘全基因组关联研究。我们比较了波多黎各人和墨西哥人这些关联的复制模式。方法：我们使用Affymetrix 6.0基因芯片对墨西哥和波多黎各三人组进行基因分型，并使用基于家族的分析来检测124个先前与哮喘相关的基因的遗传关联。结果：我们在2个人群中至少1个人群中发现了与哮喘相关的17个基因中的32个单核苷酸多态性（snp）。11个基因中22个snp与合并人群哮喘显著相关，且无显著异质性，而5个snp仅与1个人群相关，且具有统计学显著异质性。在基于基因的方法中，在合并人群中有另外2个基因与哮喘相关，另外3个基因显示出种族特异性的异质性相关。结论：我们的结果表明，只有少数遗传关联研究在我们的墨西哥和波多黎各哮喘受试者群体中是重复的。在成功复制的snp中，大多数在人群中没有显着的异质性。然而，我们发现了几个群体特有的遗传关联。[J] .中华变态反应杂志，2011;28:37-43。
Background: Although Mexicans and Puerto Ricans are jointly classified as "Hispanic/Latino," there are significant differences in asthma prevalence, severity, and mortality between the 2 groups. We sought to examine the possibility that population-specific genetic risks contribute to this disparity.Objectives: More than 100 candidate genes have been associated with asthma and replicated in an independent population, and 7 genome-wide association studies in asthma have been performed. We compared the pattern of replication of these associations in Puerto Ricans and Mexicans.Methods: We genotyped Mexican and Puerto Rican trios using an Affymetrix 6.0 GeneChip and used a family-based analysis to test for genetic associations in 124 genes previously associated with asthma.Results: We identified 32 single nucleotide polymorphisms (SNPs) in 17 genes associated with asthma in at least 1 of the 2 populations. Twenty-two of these SNPs in 11 genes were significantly associated with asthma in the combined population and showed no significant heterogeneity of association, whereas 5 SNPs were associated in only 1 population and showed statistically significant heterogeneity. In a gene-based approach 2 additional genes were associated with asthma in the combined population, and 3 additional genes displayed ethnic-specific associations with heterogeneity.Conclusions: Our results show that only a minority of genetic association studies replicate in our population of Mexican and Puerto Rican asthmatic subjects. Among SNPs that were successfully replicated, most showed no significant heterogeneity across populations. However, we identified several population-specific genetic associations. (J Allergy Clin Immunol 2011; 128: 37-43.)