The impact of genomic variants on patient response to inhaled bronchodilators: a comprehensive update

References

• Matera MG, Page CP, Calzetta L, et al. Pharmacology and therapeutics of bronchodilators revisited. Pharmacol Rev. 2020;72(1):218–252. doi:10.1124/pr.119.018150.
   PubMed Web of Science ®Google Scholar
• Sordillo JE, Kelly RS, Lutz SM, et al. Pharmacogenetics of bronchodilator response: future directions. Curr Allergy Asthma Rep. 2021;21(12):47. doi:10.1007/s11882-021-01023-w.
   PubMed Web of Science ®Google Scholar
• Baye TM, Abebe T, Wilke RA. Genotype-environment interactions and their translational implications. Per Med. 2011;8(1):59–70.
   PubMed Web of Science ®Google Scholar
• Kersten ET, Koppelman GH. Pharmacogenetics of asthma: toward precision medicine. Curr Opin Pulm Med. 2017;23(1):12–20.
   PubMed Web of Science ®Google Scholar
• Park HW, Tantisira KG, Weiss ST. Pharmacogenomics in asthma therapy: where are we and where do we go? Annu Rev Pharmacol Toxicol. 2015;55(1):129–147.
   PubMedGoogle Scholar
• Matera MG, Rinaldi B, Calzetta L, et al. Pharmacogenetic and pharmacogenomic considerations of asthma treatment. Expert Opin Drug Metab Toxicol. 2017;13(11):1159–1167. doi:10.1080/17425255.2017.1391215
   PubMed Web of Science ®Google Scholar
• Colona VL, Biancolella M, Novelli A, et al. Will GWAS eventually allow the identification of genomic biomarkers for COVID-19 severity and mortality? J Clin Invest. 2021;131(23):e155011. doi:10.1172/JCI155011
   PubMed Web of Science ®Google Scholar
• Tam V, Patel N, Turcotte M, et al. Benefits and limitations of genome-wide association studies. Nat Rev Genet. 2019;20(8):467–484. doi:10.1038/s41576-019-0127-1
   PubMed Web of Science ®Google Scholar
• Cazzola M, Page CP, Rogliani P, et al. β2-agonist therapy in lung disease. Am J Respir Crit Care Med. 2013;187(7):690–696. doi:10.1164/rccm.201209-1739PP
   PubMed Web of Science ®Google Scholar
• Litonjua AA, Gong L, Duan QL, et al. Very important pharmacogene summary ADRB2. Pharmacogenet Genomics. 2010;20(1):64–69. doi:10.1097/FPC.0b013e328333dae6
   PubMed Web of Science ®Google Scholar
• McGraw DW, Forbes SL, Kramer LA, et al. Polymorphisms of the 5’ leader cistron of the human beta2-adrenergic receptor regulate receptor expression. J Clin Invest. 1998;102(11):1927–1932. doi:10.1172/JCI4862
   PubMed Web of Science ®Google Scholar
• Zuurhout MJ, Vijverberg SJ, Raaijmakers JA, et al. Arg16 ADRB2 genotype increases the risk of asthma exacerbation in children with a reported use of long-acting β2-agonists: results of the PACMAN cohort. Pharmacogenomics. 2013;14(16):1965–1971. doi:10.2217/pgs.13.200
   PubMed Web of Science ®Google Scholar
• Nielsen AO, Jensen CS, Arredouani MS, et al. Variants of the ADRB2 gene in COPD: systematic review and meta-analyses of disease risk and treatment response. COPD. 2017;14(4):451–460. doi:10.1080/15412555.2017.1320370
   PubMedGoogle Scholar
• Billington CK, Penn RB, Hall IP. β2 Agonists. Handb Exp Pharmacol. 2017;237:23–40.
   PubMedGoogle Scholar
• Martinez FD, Graves PE, Baldini M, et al. Association between genetic polymorphisms of the beta2-adrenoceptor and response to albuterol in children with and without a history of wheezing. J Clin Invest. 1997;100(12):3184–3188. doi:10.1172/JCI119874
   PubMed Web of Science ®Google Scholar
• Silva MT, Wensing LA, Brum PC, et al. Impaired structural and functional regeneration of skeletal muscles from β2-adrenoceptor knockout mice. Acta Physiol (Oxf). 2014;211(4):617–633. doi:10.1111/apha.12329
   PubMed Web of Science ®Google Scholar
• Ortega VE. Pharmacogenetics of beta2 adrenergic receptor agonists in asthma management. Clin Genet. 2014;86(1):12–20.
   PubMed Web of Science ®Google Scholar
• Carroll CL, Stoltz P, Schramm CM, et al. β2-Adrenergic receptor polymorphisms affect response to treatment in children with severe asthma exacerbations. Chest. 2009;135(5):1186–1192. doi:10.1378/chest.08-2041
   PubMed Web of Science ®Google Scholar
• Green SA, Turki J, Innis M, et al. Amino-terminal polymorphisms of the human β2-adrenergic receptor impart distinct agonist-promoted regulatory properties. Biochemistry. 1994;33(32):9414–9419. doi:10.1021/bi00198a006
   PubMed Web of Science ®Google Scholar
• Green SA, Turki J, Bejarano P, et al. Influence of beta 2-adrenergic receptor genotypes on signal transduction in human airway smooth muscle cells. Am J Respir Cell Mol Biol. 1995;13(1):25–33. doi:10.1165/ajrcmb.13.1.7598936
   PubMed Web of Science ®Google Scholar
• Shahane G, Parsania C, Sengupta D, et al. Molecular insights into the dynamics of pharmacogenetically important N-terminal variants of the human β2-adrenergic receptor. PLoS Comput Biol. 2014;10(12):e1004006. doi:10.1371/journal.pcbi.1004006
   PubMed Web of Science ®Google Scholar
• Martinez FD, PE G, Baldini M, et al. Association between genetic polymorphisms of the beta2-adrenoceptor and response to albuterol in children with and without a history of wheezing J Clin Invest. 1997;100(12):p. 3184–3188
   PubMed Web of Science ®Google Scholar
• Israel E, Drazen JM, Liggett SB, et al. Effect of polymorphism of the β2-adrenergic receptor on response to regular use of albuterol in asthma. Int Arch Allergy Immunol. 2001;124(1–3):183–186. doi:10.1159/000053705
   PubMed Web of Science ®Google Scholar
• Israel E, Chinchilli VM, Ford JG, et al. Use of regularly scheduled albuterol treatment in asthma: genotype-stratified, randomised, placebo-controlled cross-over trial. Lancet. 2004;364(9444):1505–1512. doi:10.1016/S0140-6736(04)17273-5
   PubMed Web of Science ®Google Scholar
• Israel E, Drazen JM, Liggett SB, et al. The effect of polymorphisms of the β2-adrenergic receptor on the response to regular use of albuterol in asthma. Am J Respir Crit Care Med. 2000;162(1):75–80. doi:10.1164/ajrccm.162.1.9907092
   PubMed Web of Science ®Google Scholar
• Wechsler ME, Lehman E, Lazarus SC, et al. β-Adrenergic receptor polymorphisms and response to salmeterol. Am J Respir Crit Care Med. 2006;173(5):519–526. doi:10.1164/rccm.200509-1519OC
   PubMed Web of Science ®Google Scholar
• Palmer CN, Lipworth BJ, Lee S, et al. Arginine-16 β2 adrenoceptor genotype predisposes to exacerbations in young asthmatics taking regular salmeterol. Thorax. 2006;61(11):940–944. doi:10.1136/thx.2006.059386
   PubMed Web of Science ®Google Scholar
• Lee DK, Currie GP, Hall IP, et al. The arginine-16 β2-adrenoceptor polymorphism predisposes to bronchoprotective subsensitivity in patients treated with formoterol and salmeterol. Br J Clin Pharmacol. 2004;57(1):68–75. doi:10.1046/j.1365-2125.2003.01955.x
   PubMed Web of Science ®Google Scholar
• Wechsler ME, Kunselman SJ, Chinchilli VM, et al. Effect of β2-adrenergic receptor polymorphism on response to longacting β2 agonist in asthma (LARGE trial): a genotype-stratified, randomised, placebo-controlled, crossover trial. Lancet. 2009;374(9703):1754–1764. doi:10.1016/S0140-6736(09)61492-6
   PubMed Web of Science ®Google Scholar
• Bleecker ER, Nelson HS, Kraft M, et al. β2-Receptor polymorphisms in patients receiving salmeterol with or without fluticasone propionate. Am J Respir Crit Care Med. 2010;181(7):676–687. doi:10.1164/200809-1511OC
   PubMed Web of Science ®Google Scholar
• Bonini M, Permaul P, Kulkarni T, et al. Loss of salmeterol bronchoprotection against exercise in relation to ADRB2 Arg16Gly polymorphism and exhaled nitric oxide. Am J Respir Crit Care Med. 2013;188(12):1407–1412. doi:10.1164/rccm.201307-1323OC
   PubMed Web of Science ®Google Scholar
• Snyder EM, Beck KC, Dietz NM, et al. Influence of β2-adrenergic receptor genotype on airway function during exercise in healthy adults. Chest. 2006;129(3):762–770. doi:10.1378/chest.129.3.762
   PubMed Web of Science ®Google Scholar
• Hikino K, Kobayashi S, Ota E, et al. A meta-analysis of the influence of ADRB2 genetic polymorphisms on albuterol (salbutamol) therapy in patients with asthma. Br J Clin Pharmacol. 2021;87(4):p. 1708–1716.
   PubMed Web of Science ®Google Scholar
• Bleecker ER, Meyers DA, Bailey WC, et al. ADRB2 polymorphisms and budesonide/formoterol responses in COPD. Chest. 2012;142(2):320–328. doi:10.1378/chest.11-1655
   PubMed Web of Science ®Google Scholar
• Rabe KF, Fabbri LM, Israel E, et al. Effect of ADRB2 polymorphisms on the efficacy of salmeterol and tiotropium in preventing COPD exacerbations: a prespecified substudy of the POET-COPD trial. Lancet Respir Med. 2014;2(1):44–53. doi:10.1016/S2213-2600(13)70248-0
   PubMed Web of Science ®Google Scholar
• Karimi L, Lahousse L, Ghanbari M, et al. β2-Adrenergic receptor (ADRB2) gene polymorphisms and risk of COPD exacerbations: the Rotterdam study. J Clin Med. 2019;8(11):p. 1835.
   PubMed Web of Science ®Google Scholar
• Yelensky R, Li Y, Lewitzky S, et al. A pharmacogenetic study of ADRB2 polymorphisms and indacaterol response in COPD patients. Pharmacogenomics J. 2012 Dec;12(6):484–488.
   PubMed Web of Science ®Google Scholar
• Turner S, Francis B, Vijverberg S, et al. Childhood asthma exacerbations and the Arg16 β2-receptor polymorphism: a meta-analysis stratified by treatment. J Allergy Clin Immunol. 2016;138(1):107–113. doi:10.1016/j.jaci.2015.10.045
   PubMed Web of Science ®Google Scholar
• Slob EMA, Vijverberg SJH, Palmer CNA, et al. Pharmacogenetics of inhaled long-acting beta2-agonists in asthma: a systematic review. Pediatr Allergy Immunol. 2018;29(7):705–714. doi:10.1111/pai.12956
   PubMed Web of Science ®Google Scholar
• Giubergia V, Gravina LP, Castaños C, et al. Influence of β2-adrenoceptor polymorphisms on the response to chronic use of albuterol in asthmatic children. Pediatr Pulmonol. 2008;43(5):421–425. doi:10.1002/ppul.20759
   PubMed Web of Science ®Google Scholar
• Lee MY, Cheng SN, Chen SJ, et al. Polymorphisms of the β2-adrenergic receptor correlated to nocturnal asthma and the response of terbutaline nebulizer. Pediatr Neonatol. 2011;52(1):18–23. doi:10.1016/j.pedneo.2010.12.011
   PubMed Web of Science ®Google Scholar
• Bhosale S, Nikte SV, Sengupta D, et al. Differential dynamics underlying the Gln27Glu population variant of the β2-adrenergic receptor. J Membr Biol. 2019;252(4–5):499–507. doi:10.1007/s00232-019-00093-2
   PubMed Web of Science ®Google Scholar
• Mohamed-Hussein AAR, Sayed SS, Eldien HMS, et al. Beta 2 adrenergic receptor genetic polymorphisms in bronchial asthma: relationship to disease risk, severity, and treatment response. Lung. 2018;196(6):673–680. doi:10.1007/s00408-018-0153-3
   PubMed Web of Science ®Google Scholar
• Alghobashy AA, Elsharawy SA, Alkholy UM, et al. B2 adrenergic receptor gene polymorphism effect on childhood asthma severity and response to treatment. Pediatr Res. 2018;83(3):597–605. doi:10.1038/pr.2017.304
   PubMed Web of Science ®Google Scholar
• Abood HA. Impact of 27gln\glu polymorphisms of β2-adrenergic receptor gene on pulmonary function in asthmatic children treated with nebulized salbutamol. Biomed Biotechnol Res J. 2021;5(4):435–439.
   Google Scholar
• Scaparrotta A, Franzago M, Marcovecchio ML, et al. Role of THRB, ARG1, and ADRB2 genetic variants on bronchodilators response in asthmatic children. J Aerosol Med Pulm Drug Deliv. 2019;32(3):164–173. doi:10.1089/jamp.2018.1493
   PubMed Web of Science ®Google Scholar
• Martin AC, Zhang G, Rueter K, et al. β2-adrenoceptor polymorphisms predict response to β2-agonists in children with acute asthma. J Asthma. 2008;45(5):383–388. doi:10.1080/02770900801971792
   PubMed Web of Science ®Google Scholar
• Bleecker ER, Yancey SW, Baitinger LA, et al. Salmeterol response is not affected by beta2-adrenergic receptor genotype in subjects with persistent asthma. J Allergy Clin Immunol. 2006;118(4):809–816. doi:10.1016/j.jaci.2006.06.036
   PubMed Web of Science ®Google Scholar
• Petrovic-Stanojevic N, Topic A, Nikolic A, et al. Polymorphisms of beta2-adrenergic receptor gene in Serbian asthmatic adults: effects on response to beta-agonists. Mol Diagn Ther. 2014;18(6):639–646. doi:10.1007/s40291-014-0116-1
   PubMed Web of Science ®Google Scholar
• Soleimani F, Fahimi F, Adimi Naghan P, et al. The effect of polymorphisms of beta2 adrenoceptors on response to long-acting beta2 agonists in Iranian asthmatic patients. Iran J Allergy Asthma Immunol. 2013;12(4):383–390.
   PubMed Web of Science ®Google Scholar
• Green SA, Cole G, Jacinto M, et al. A polymorphism of the human β2-adrenergic receptor within the fourth transmembrane domain alters ligand binding and functional properties of the receptor. J Biol Chem. 1993;268(31):23116–23121. doi:10.1016/S0021-9258(19)49434-9
   PubMed Web of Science ®Google Scholar
• Small KM, McGraw DW, Liggett SB. Pharmacology and physiology of human adrenergic receptor polymorphisms. Annu Rev Pharmacol Toxicol. 2003;43(1):381–411.
   PubMedGoogle Scholar
• Green SA, Rathz DA, Schuster AJ, et al. The Ile164 β2-adrenoceptor polymorphism alters salmeterol exosite binding and conventional agonist coupling to Gs. Eur J Pharmacol. 2001;421(3):141–147. doi:10.1016/S0014-2999(01)01049-4
   PubMed Web of Science ®Google Scholar
• Bandaru S, Tarigopula P, Akka J, et al. Association of Beta 2 adrenergic receptor (Thr164ile) polymorphism with salbutamol refractoriness in severe asthmatics from Indian population. Gene. 2016;592(1):15–22. doi:10.1016/j.gene.2016.07.043
   PubMed Web of Science ®Google Scholar
• Ortega VE, Hawkins GA, Moore WC, et al. Effect of rare variants in ADRB2 on risk of severe exacerbations and symptom control during longacting β agonist treatment in a multiethnic asthma population: a genetic study. Lancet Respir Med. 2014;2(3):204–213. doi:10.1016/S2213-2600(13)70289-3
   PubMed Web of Science ®Google Scholar
• Condreay LD, Chiano MN, Li L, et al. ADRB2 p.Thr164Ile association with hospitalization depends upon asthma severity. J Allergy Clin Immunol. 2019;143(5):1962–1965. doi:10.1016/j.jaci.2019.01.012
   PubMed Web of Science ®Google Scholar
• Lima JJ. Do genetic polymorphisms alter patient response to inhaled bronchodilators? Expert Opin Drug Metab Toxicol. 2014;10(9):1231–1240.
   PubMed Web of Science ®Google Scholar
• Small KM, Brown KM, Theiss CT, et al. An Ile to Met polymorphism in the catalytic domain of adenylyl cyclase type 9 confers reduced β2-adrenergic receptor stimulation. Pharmacogenetics. 2003;13(9):535–541. doi:10.1097/00008571-200309000-00002
   PubMedGoogle Scholar
• Tantisira KG, Small KM, Litonjua AA, et al. Molecular properties and pharmacogenetics of a polymorphism of adenylyl cyclase type 9 in asthma: interaction between β-agonist and corticosteroid pathways. Hum Mol Genet. 2005;14(12):1671–1677. doi:10.1093/hmg/ddi175
   PubMed Web of Science ®Google Scholar
• Kim SH, Ye YM, Lee HY, et al. Combined pharmacogenetic effect of ADCY9 and ADRB2 gene polymorphisms on the bronchodilator response to inhaled combination therapy. J Clin Pharm Ther. 2011;36(3):399–405. doi:10.1111/j.1365-2710.2010.01196.x
   PubMed Web of Science ®Google Scholar
• Ortega VE, Meyers DA, Bleecker ER. Asthma pharmacogenetics and the development of genetic profiles for personalized medicine. Pharmgenomics Pers Med. 2015;8:9–22.
   PubMedGoogle Scholar
• Poon AH, Tantisira KG, Litonjua AA, et al. Association of corticotropin-releasing hormone receptor-2 genetic variants with acute bronchodilator response in asthma. Pharmacogenet Genomics. 2008;18(5):373–382. doi:10.1097/FPC.0b013e3282fa760a
   PubMed Web of Science ®Google Scholar
• Litonjua AA, Lasky-Su J, Schneiter K, et al. ARG1 is a novel bronchodilator response gene: screening and replication in four asthma cohorts. Am J Respir Crit Care Med. 2008;178(7):688–694. doi:10.1164/rccm.200709-1363OC
   PubMed Web of Science ®Google Scholar
• García-Menaya JM, Cordobés-Durán C, García-Martín E, et al. Pharmacogenetic factors affecting asthma treatment response. Potential implications for drug therapy. Front Pharmacol. 2019;10:520.
   PubMed Web of Science ®Google Scholar
• Duan QL, Gaume BR, Hawkins GA, et al. Regulatory haplotypes in ARG1 are associated with altered bronchodilator response. Am J Respir Crit Care Med. 2011;183(4):449–454. doi:10.1164/rccm.201005-0758OC
   PubMed Web of Science ®Google Scholar
• Vonk JM, Postma DS, Maarsingh H, et al. Arginase 1 and arginase 2 variations associate with asthma, asthma severity and β2 agonist and steroid response. Pharmacogenet Genomics. 2010;20(3):179–186. doi:10.1097/FPC.0b013e328336c7fd
   PubMed Web of Science ®Google Scholar
• Iordanidou M, Paraskakis E, Tavridou A, et al. G894T polymorphism of eNOS gene is a predictor of response to combination of inhaled corticosteroids with long-lasting β2-agonists in asthmatic children. Pharmacogenomics. 2012;13(12):1363–1372. doi:10.2217/pgs.12.120
   PubMed Web of Science ®Google Scholar
• Panebra A, Schwarb MR, Glinka CB, et al. Heterogeneity of transcription factor expression and regulation in human airway epithelial and smooth muscle cells. Am J Physiol Lung Cell Mol Physiol. 2007;293(2):L453–L462. doi:10.1152/ajplung.00084.2007
   PubMed Web of Science ®Google Scholar
• Duan QL, Du R, Lasky-Su J, et al. A polymorphism in the thyroid hormone receptor gene is associated with bronchodilator response in asthmatics. Pharmacogenomics J. 2013;13(2):130–136. doi:10.1038/tpj.2011.56
   PubMed Web of Science ®Google Scholar
• Himes BE, Jiang X, Hu R, et al. Genome-wide association analysis in asthma subjects identifies SPATS2L as a novel bronchodilator response gene. PLoS Genet. 2012;8(7):e1002824. doi:10.1371/journal.pgen.1002824
   PubMed Web of Science ®Google Scholar
• Brehm JM, Ramratnam SK, Tse SM, et al. Stress and bronchodilator response in children with asthma. Am J Respir Crit Care Med. 2015;192(1):47–56. doi:10.1164/rccm.201501-0037OC
   PubMed Web of Science ®Google Scholar
• Drysdale CM, McGraw DW, Stack CB, et al. Complex promoter and coding region β2-adrenergic receptor haplotypes alter receptor expression and predict in vivo responsiveness. Proc Natl Acad Sci U S A. 2000;97(19):10483–10488. doi:10.1073/pnas.97.19.10483
   PubMed Web of Science ®Google Scholar
• Zhang L, Zheng J, Wang H, et al. Association of β2-adrenoceptor polymorphisms with asthma risk and therapeutic response: a meta-analysis and systematic review. Int J Clin Exp Med. 2018;11(4):3905–3923.
   Web of Science ®Google Scholar
• Tellería JJ, Blanco-Quirós A, Muntión S, et al. Tachyphylaxis to β2-agonists in Spanish asthmatic patients could be modulated by β2-adrenoceptor gene polymorphisms. Respir med. 2006;100(6):1072–1078. doi:10.1016/j.rmed.2005.09.028
   PubMed Web of Science ®Google Scholar
• Moore PE, Laporte JD, Abraham JH, et al. Polymorphism of the β2-adrenergic receptor gene and desensitization in human airway smooth muscle. Am J Respir Crit Care Med. 2000;162(6):2117–2124. doi:10.1164/ajrccm.162.6.9909046
   PubMed Web of Science ®Google Scholar
• Qiu YY, Zhang XL, Qin Y, et al. Beta2-adrenergic receptor haplotype/polymorphisms and asthma susceptibility and clinical phenotype in a Chinese Han population. Allergy Asthma Proc. 2010;31(5):91–97. doi:10.2500/aap.2010.31.3371
   PubMed Web of Science ®Google Scholar
• Limsuwan T, Thakkinstian A, Verasertniyom O, et al. Possible protective effects of the Glu27 allele of beta2-adrenergic receptor polymorphism in Thai asthmatic patients. Asian Pac J Allergy Immunol. 2010;28(2–3):107–114.
   PubMed Web of Science ®Google Scholar
• Jovicic N, Babic T, Dragicevic S, et al. ADRB2 gene polymorphisms and salbutamol responsiveness in Serbian children with asthma. Balkan J Med Genet. 2018;21(1):33–38. doi:10.2478/bjmg-2018-0007
   PubMed Web of Science ®Google Scholar
• Toraih EA, Hussein MH, Ibrahim A, et al. Beta2-adrenergic receptor variants in children and adolescents with bronchial asthma. Front Biosci (Elite Ed). 2019;11(1):61–78. doi:10.2741/e846
   Google Scholar
• Hizawa N, Makita H, Nasuhara Y, et al. β2-adrenergic receptor genetic polymorphisms and short-term bronchodilator responses in patients with COPD. Chest. 2007;132(5):1485–1492. doi:10.1378/chest.07-1103
   PubMed Web of Science ®Google Scholar
• Cazzola M, Page C, Matera MG. Long-acting muscarinic receptor antagonists for the treatment of respiratory disease. Pulm Pharmacol Ther. 2013;26(3):307–317.
   PubMed Web of Science ®Google Scholar
• Matera MG, Cazzola M. Muscarinic receptor antagonists. Handb Exp Pharmacol. 2017;237:41–62.
   PubMedGoogle Scholar
• Donfack J, Kogut P, Forsythe S, et al. Sequence variation in the promoter region of the cholinergic receptor muscarinic 3 gene and asthma and atopy. J Allergy Clin Immunol. 2003;111(3):527–532. doi:10.1067/mai.2003.71
   PubMed Web of Science ®Google Scholar
• Jiménez-Morales S, Jiménez-Ruíz JL, Del Río-Navarro BE, et al. CHRM2 but not CHRM1 or CHRM3 polymorphisms are associated with asthma susceptibility in Mexican patients. Mol Biol Rep. 2014;41(4):2109–2117. doi:10.1007/s11033-014-3060-6
   PubMed Web of Science ®Google Scholar
• Michel MC, Teitsma CA. Polymorphisms in human muscarinic receptor subtype genes. Handb Exp Pharmacol. 2012;208:49–59.
   Google Scholar
• Chukhlovin A, Titova O, Yolshin N, et al. Increased expression of ADRB2, CHRM3 and glucocorticoid alpha receptor genes in blood leukocytes of COPD patients. Eur Respir J. 2016;48:A5059.
   Web of Science ®Google Scholar
• Szczepankiewicz A, Breborowicz A, Sobkowiak P, et al. Association of A/T polymorphism of the CHRM2 gene with bronchodilator response to ipratropium bromide in asthmatic children. Adv Respir Med. 2009;77(1):5–10. doi:10.5603/ARM.27847
   Google Scholar
• Cherubini E, Esposito MC, Scozzi D, et al. Genetic polymorphism of CHRM2 in COPD: clinical significance and therapeutic implications. J Cell Physiol. 2016;231(8):1745–1751. doi:10.1002/jcp.25277
   PubMed Web of Science ®Google Scholar
• Park HW, Yang MS, Park CS, et al. Additive role of tiotropium in severe asthmatics and Arg16Gly in ADRB2 as a potential marker to predict response. Allergy. 2009;64(5):778–783. doi:10.1111/j.1398-9995.2008.01876.x
   PubMed Web of Science ®Google Scholar
• Yoshikawa T, Kanazawa H. Functional crosstalk between β2-adrenoreceptor and muscarinic acetylcholine receptor: implications for gene-gene interactions and bronchodilatory responses in patients with asthma and COPD. Curr Pharmacogenomics Person Med. 2008;6(4):302–319.
   Google Scholar
• Condreay L, Huang L, Harris E, et al. Genetic effects on treatment response of umeclidinium/vilanterol in chronic obstructive pulmonary disease. Respir med. 2016;114:123–126.
   PubMed Web of Science ®Google Scholar
• Hosking L, Yeo A, Hoffman J, et al. Genetics plays a limited role in predicting chronic obstructive pulmonary disease treatment response and exacerbation. Respir med. 2021;187:106573.
   PubMed Web of Science ®Google Scholar
• Blake K, Madabushi R, Derendorf H, et al. Population pharmacodynamic model of bronchodilator response to inhaled albuterol in children and adults with asthma. Chest. 2008;134(5):981–989. doi:10.1378/chest.07-2991
   PubMed Web of Science ®Google Scholar
• Cazzola M, Rogliani P, Sanduzzi A, et al. Influence of ethnicity on response to asthma drugs. Expert Opin Drug Metab Toxicol. 2015;11(7):1089–1097. doi:10.1517/17425255.2015.1047341
   PubMed Web of Science ®Google Scholar
• Cazzola M, Calzetta L, Matera MG, et al. How does race/ethnicity influence pharmacological response to asthma therapies? Expert Opin Drug Metab Toxicol. 2018;14(4):435–446. doi:10.1080/17425255.2018.1449833
   PubMed Web of Science ®Google Scholar
• EMBL-EBI. rs1042713 SNP. Ensembl release 109; 2023. Available from: https://www.ensembl.org/Homo_sapiens/Variation/Population?db=core;r=5:148826377-148827377;v=rs1042713;vdb=variation;vf=166041816
   Google Scholar
• EMBL-EBI. rs1042714 SNP. Ensembl release 109; 2023. Available from: https://www.ensembl.org/Homo_sapiens/Variation/Population?db=core;r=5:148826410-148827410;v=rs1042714;vdb=variation;vf=166041919
   Google Scholar
• EMBL-EBI. rs1800888 SNP. Ensembl release 109; 2023. Available from: https://www.ensembl.org/Homo_sapiens/Variation/Population?db=core;r=5:148826822-148827822;v=rs1800888;vdb=variation;vf=166342499
   Google Scholar
• Choudhry S, Que LG, Yang Z, et al. GSNO reductase and β2-adrenergic receptor gene-gene interaction: bronchodilator responsiveness to albuterol. Pharmacogenet Genomics. 2010;20(6):351–358. doi:10.1097/FPC.0b013e328337f992
   PubMed Web of Science ®Google Scholar
• Spear ML, Hu D, Pino-Yanes M, et al. A genome-wide association and admixture mapping study of bronchodilator drug response in African Americans with asthma. Pharmacogenomics J. 2019;19(3):249–259. doi:10.1038/s41397-018-0042-4
   PubMed Web of Science ®Google Scholar
• Padhukasahasram B, Yang JJ, Levin AM, et al. Gene-based association identifies SPATA13-AS1 as a pharmacogenomic predictor of inhaled short-acting beta-agonist response in multiple population groups. Pharmacogenomics J. 2014;14(4):365–371. doi:10.1038/tpj.2013.49
   PubMed Web of Science ®Google Scholar
• Mak ACY, White MJ, Eckalbar WL, et al. Whole-genome sequencing of pharmacogenetic drug response in racially diverse children with asthma. Am J Respir Crit Care Med. 2018;197(12):1552–1564. doi:10.1164/rccm.201712-2529OC
   PubMed Web of Science ®Google Scholar
• Wechsler ME, Yawn BP, Fuhlbrigge AL, et al. Anticholinergic vs long-acting β-agonist in combination with inhaled corticosteroids in black adults with asthma: the BELT randomized clinical trial. JAMA. 2015;314(16):1720–1730. doi:10.1001/jama.2015.13277
   PubMed Web of Science ®Google Scholar
• Voorhies K, Sordillo JE, McGeachie M, et al. Age by single nucleotide polymorphism interactions on bronchodilator response in asthmatics. J Pers Med. 2021;11(1):59. doi:10.3390/jpm11010059.
   PubMed Web of Science ®Google Scholar
• McDaneld TG, Hancock DL, Moody DE. Altered mRNA abundance of ASB15 and four other genes in skeletal muscle following administration of beta-adrenergic receptor agonists. Physiol Genomics. 2004;16(2):275–283.
   PubMed Web of Science ®Google Scholar
• Sordillo JE, McGeachie M, Lutz SM, et al. Longitudinal analysis of bronchodilator response in asthmatics and effect modification of age-related trends by genotype. Pediatr Pulmonol. 2019;54(2):158–164. doi:10.1002/ppul.24219
   PubMed Web of Science ®Google Scholar
• Soto-Palma C, Niedernhofer LJ, Faulk CD, et al. Epigenetics, DNA damage, and aging. J Clin Invest. 2022;132(16):e158446. doi:10.1172/JCI158446
   PubMed Web of Science ®Google Scholar
• Primorac D, Bach-Rojecky L, Vađunec D, et al. Pharmacogenomics at the center of precision medicine: challenges and perspective in an era of Big Data. Pharmacogenomics. 2020;21(2):141–156. doi:10.2217/pgs-2019-0134
   PubMed Web of Science ®Google Scholar
• Novelli G, Biancolella M, Latini A, et al. Precision medicine in non-communicable diseases. High Throughput. 2020;9(1):3. doi:10.3390/ht9010003
   PubMedGoogle Scholar
• Wake DT, Ilbawi N, Dunnenberger HM, et al. Pharmacogenomics: prescribing precisely. Med Clin North Am. 2019;103(6):977–990. doi:10.1016/j.mcna.2019.07.002
   PubMed Web of Science ®Google Scholar
• Muraro A, Lemanske RF Jr, Hellings PW, et al. Precision medicine in patients with allergic diseases: airway diseases and atopic dermatitis-PRACTALL document of the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma & Immunology. J Allergy Clin Immunol. 2016;137(5):1347–1358. doi:10.1016/j.jaci.2016.03.010
   PubMed Web of Science ®Google Scholar
• Singh DB. The impact of pharmacogenomics in personalized medicine. Adv Biochem Eng Biotechnol. 2020;171:369–394.
   PubMed Web of Science ®Google Scholar
• Manzoni C, Kia DA, Vandrovcova J, et al. Genome, transcriptome and proteome: the rise of omics data and their integration in biomedical sciences. Brief Bioinform. 2018;19(2):286–302. doi:10.1093/bib/bbw114
   PubMed Web of Science ®Google Scholar
• Latini A, Borgiani P, Novelli G, et al. miRnas in drug response variability: potential utility as biomarkers for personalized medicine. Pharmacogenomics. 2019;20(14):1049–1059. doi:10.2217/pgs-2019-0089
   PubMed Web of Science ®Google Scholar
• Kelly RS, Sordillo JE, Lutz SM, et al. Pharmacometabolomics of bronchodilator response in asthma and the role of age-metabolite interactions. Metabolites. 2019;9(9):179. doi:10.3390/metabo9090179
   PubMed Web of Science ®Google Scholar
• Cardenas A, Sordillo JE, Rifas-Shiman SL, et al. The nasal methylome as a biomarker of asthma and airway inflammation in children. Nat Commun. 2019;10(1):3095. doi:10.1038/s41467-019-11058-3
   PubMed Web of Science ®Google Scholar