A genome-wide analysis of the response to inhaled β2-agonists in chronic obstructive pulmonary disease

Pharmacogenomics J. 2016 Aug;16(4):326-35. doi: 10.1038/tpj.2015.65. Epub 2015 Oct 27.

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.

Publication types

  • Meta-Analysis
  • Multicenter Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adrenergic beta-2 Receptor Agonists / therapeutic use*
  • African Americans / genetics
  • Aged
  • Bronchodilator Agents / therapeutic use*
  • Cadherins / genetics
  • Europe
  • Female
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Lung / drug effects*
  • Lung / physiopathology
  • Male
  • Middle Aged
  • New Zealand
  • North America
  • Pharmacogenomic Testing
  • Pharmacogenomic Variants / genetics*
  • Phenotype
  • Potassium Channels, Inwardly Rectifying / genetics
  • Potassium Channels, Tandem Pore Domain / genetics
  • Pulmonary Disease, Chronic Obstructive / diagnosis
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Pulmonary Disease, Chronic Obstructive / genetics*
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Risk Factors
  • Sarcoglycans / genetics
  • Severity of Illness Index
  • Spirometry
  • Treatment Outcome
  • Whites / genetics

Substances

  • Adrenergic beta-2 Receptor Agonists
  • Bronchodilator Agents
  • Cadherins
  • H-cadherin
  • KCNJ2 protein, human
  • KCNK1 protein, human
  • Potassium Channels, Inwardly Rectifying
  • Potassium Channels, Tandem Pore Domain
  • SGCD protein, human
  • Sarcoglycans