Center for Child Health Care Studies, Department of Population Medicine, Harvard Pilgrim Health Care Institute and Harvard Medical School, Boston, Mass; Department of Pediatrics, Children's Hospital, Boston, Mass; Harvard Medical School, Boston, Mass.
Harvard Medical School, Boston, Mass; Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Boston, Mass; Center for Genomic Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Mass.
J Allergy Clin Immunol. 2014 Mar;133(3):723-8.e3. doi: 10.1016/j.jaci.2013.09.037. Epub 2013 Nov 23.
Single nucleotide polymorphisms (SNPs) influence a patient's response to inhaled corticosteroids and β2-agonists, and the effect of treatment with inhaled corticosteroids is synergistic with the effect of β2-agonists. We hypothesized that use of inhaled corticosteroids could influence the effect of SNPs associated with a bronchodilator response.
To assess whether, among subjects with asthma, the association of SNPs with bronchodilator response is different between those treated with inhaled corticosteroids versus those on placebo.
A genome-wide association analysis was conducted by using 581 white subjects from the Childhood Asthma Management Program. By using data for 449,540 SNPs, we conducted a gene by environment analysis in PLINK with inhaled corticosteroid treatment as the environmental exposure and bronchodilator response as the outcome measure. We attempted to replicate the top 12 SNPs in the Leukotriene Modifier or Corticosteroid or Corticosteroid-Salmeterol Trial.
The combined P value for the Childhood Asthma Management Program and Leukotriene Modifier or Corticosteroid or Corticosteroid-Salmeterol Trial populations was 4.8 × 10(-8) for rs3752120, which is located in the zinc finger protein gene ZNF432 and has an unknown function.
Inhaled corticosteroids appear to modulate the association of bronchodilator response with variant(s) in the ZNF432 gene among adults and children with asthma.
单核苷酸多态性（SNP）影响患者对吸入皮质类固醇和β2-激动剂的反应，吸入皮质类固醇的治疗效果与β2-激动剂的效果具有协同作用。我们假设，吸入皮质类固醇的使用可能会影响与支气管扩张剂反应相关的 SNP 的作用。
评估在哮喘患者中，与吸入皮质类固醇治疗相比，SNP 与支气管扩张剂反应的相关性在使用吸入皮质类固醇治疗的患者和使用安慰剂的患者之间是否存在差异。
通过使用来自儿童哮喘管理计划的 581 名白种人受试者进行全基因组关联分析。通过使用 449540 个 SNP 的数据，我们在 PLINK 中进行了基因与环境分析，将吸入皮质类固醇治疗作为环境暴露，将支气管扩张剂反应作为结局测量。我们试图在白三烯调节剂或皮质类固醇或皮质类固醇-沙美特罗试验中复制前 12 个 SNP。
儿童哮喘管理计划和白三烯调节剂或皮质类固醇或皮质类固醇-沙美特罗试验人群的综合 P 值为 4.8×10(-8)，这与位于锌指蛋白基因 ZNF432 中的 rs3752120 相关，该 SNP 具有未知功能。
吸入皮质类固醇似乎调节了支气管扩张剂反应与 ZNF432 基因中的变异（S）之间的关联，这在成人和儿童哮喘患者中均存在。
