Abstract
Background: Differences in response to long-acting beta agonists (LABA) between individuals with asthma from different ethnic groups and the lack of pharmacogenetic studies in minorities provide the rationale for pharmacogenetic studies.
Objectives: To identify genetic determinants of LABA response in individuals with asthma across diverse ancestral backgrounds.
Methods: We genotyped 1,375 non-Hispanic Whites (NHW) randomized to different ICS and LABA combinations from the COMPASS trial (Kuna Int J Clin Pract 2007) and 483 African Americans from a formoterol/budesonide trial (239 randomized to LABA, Brown J Allergy Clin Immunol 2012, AA LABA) with the Illumina whole-genome Arrays. We performed GWAS for asthma exacerbations using logistic regression and time-to-exacerbation GWAS (Syed BMC Bioinformatics 2017) in AA LABA to evaluate genotype-by-LABA/placebo arm interactions.
Results: In COMPASS NHW, we identified associations adjacent to ZKSCAN2 (rs16974591, p=6.9x10-8) and FOXP1 (rs6766000, p=8.6x10-8). LABA-genotype interaction GWAS of AA LABA identified subthreshold associations adjacent to TBC1D1 (rs7681241, pinteraction=9.3x10-6) and in ITPRID1 (rs4720044, pinteraction=2.6x10-5). Time-to-event GWAS in AA LABA identified subthreshold associations in MORN1 (rs75230941, p=7.7x10-6) and PLCB1 (rs60800602, p=1.4x10-5).
Conclusions: GWAS identified plausible pharmacogenetic loci requiring replication including FOXP1 whose deletion in airway epithelium results in airway hyperresponsiveness (Li J Clin Invest 2016), an asthma epigenetic locus (TBC1D1, Hoang Eur Respir J 2020), and albuterol response locus in African descent minorities (PLCB1, Mak Am J Respir Crit Care Med 2018).
Footnotes
Cite this article as: European Respiratory Journal 2021; 58: Suppl. 65, PA886.
This abstract was presented at the 2021 ERS International Congress, in session “Prediction of exacerbations in patients with COPD”.
This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).
- Copyright ©the authors 2021