A genome-wide analysis of the response to inhaled β2-agonists in chronic obstructive pulmonary disease.
A genome-wide analysis of the response to inhaled β2-agonists in chronic obstructive pulmonary disease.
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DOI：
10.1038/tpj.2015.65
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发表时间：
2016-08
期刊：
影响因子：
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通讯作者：
COPDGene Investigators—clinical centers
中科院分区：
文献类型：
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作者：
Hardin M;Cho MH;McDonald ML;Wan E;Lomas DA;Coxson HO;MacNee W;Vestbo J;Yates JC;Agusti A;Calverley PM;Celli B;Crim C;Rennard S;Wouters E;Bakke P;Bhatt SP;Kim V;Ramsdell J;Regan EA;Make BJ;Hokanson JE;Crapo JD;Beaty TH;Hersh CP;ECLIPSE and COPDGene Investigators;COPDGene Investigators—clinical centers
短效β2受体激动剂是治疗慢性阻塞性肺疾病（COPD）最常用的药物。尚未确定决定COPD患者支气管扩张剂反应性（BDR）的遗传变异。我们在一个非洲裔美国人和四个白色人群中的5789名患有COPD的当前或以前的吸烟者中进行了BDR的全基因组关联研究（GWAS）。BDR定义为对吸入β2-受体激动剂的定量肺量计反应。我们在荟萃分析中合并了结果。在荟萃分析中，基因KCNK 1（P=2.02×10−7）和KCNJ 2（P=1.79×10−7）中的SNP与BDR的关联最大。在非裔美国人中，CDH 13的SNP与BDR显著相关（P=5.1×10−9）。在所有受试者中，在基于基因的分析中确定了与CDH 13的名义关联。我们确定了COPD受试者中两个钾通道基因（KCNK 1和KCNJ 2）附近的变异与BDR的暗示性关联。CDH 13中的SNP与非裔美国人的BDR显著相关。
Short-acting β2-agonist bronchodilators are the most common medications used in treating chronic obstructive pulmonary disease (COPD). Genetic variants determining bronchodilator responsiveness (BDR) in COPD have not been identified. We performed a genome-wide association study (GWAS) of BDR in 5789 current or former smokers with COPD in one African American and four white populations. BDR was defined as the quantitative spirometric response to inhaled β2-agonists. We combined results in a meta-analysis. In the meta-analysis, SNPs in the genes KCNK1 (P=2.02×10−7) and KCNJ2 (P=1.79×10−7) were the top associations with BDR. Among African Americans, SNPs in CDH13 were significantly associated with BDR (P=5.1×10−9). A nominal association with CDH13 was identified in a gene-based analysis in all subjects. We identified suggestive association with BDR among COPD subjects for variants near two potassium channel genes (KCNK1 and KCNJ2). SNPs in CDH13 were significantly associated with BDR in African Americans.