1. A genome-wide analysis of the response to inhaled β2-agonists in chronic obstructive pulmonary disease.
- Author
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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, and Hersh CP
- Subjects
- Black or African American genetics, Aged, Cadherins genetics, Europe, Female, Genome-Wide Association Study, Genotype, Humans, Lung physiopathology, Male, Middle Aged, New Zealand, North America, Pharmacogenomic Testing, Phenotype, Potassium Channels, Inwardly Rectifying genetics, Potassium Channels, Tandem Pore Domain genetics, Pulmonary Disease, Chronic Obstructive diagnosis, Pulmonary Disease, Chronic Obstructive physiopathology, Risk Factors, Sarcoglycans genetics, Severity of Illness Index, Spirometry, Treatment Outcome, White People genetics, Adrenergic beta-2 Receptor Agonists therapeutic use, Bronchodilator Agents therapeutic use, Lung drug effects, Pharmacogenomic Variants genetics, Pulmonary Disease, Chronic Obstructive drug therapy, Pulmonary Disease, Chronic Obstructive genetics
- Abstract
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, single-nucleotide polymorphisms (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.The Pharmacogenomics Journal advance online publication, 27 October 2015; doi:10.1038/tpj.2015.65.
- Published
- 2016
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