Pharmacogenomic of asthma in children
Abstract
Asthma is an inflammatory airway disease characterized by bronchial hyper-responsiveness, reversible airflow limitation, and respiratory symptoms. Asthma affects 300 million people in developed countries. More than 10% of asthma complaints in children occur at school age. Asthma therapy in children using pharmacological agents is still the main choice until now. However, the response of pediatric patients to asthma treatment varies. In addition to age, organ function, and drug interactions, genetic factors are often associated with drug response variability. This variability can occur due to single nucleotide polymorphisms (SNP) in protein-coding genes that play a role in bioavailability and drug response. Understanding of pharmacogenomics as the basis of individualized medicine aims to avoid adverse drug reactions and maximize drug effectiveness. The existence of genetic variation allows the drug response between individuals to be different. Pharmacogenomics provides important information in individual-based medicine so that it can predict the existence of a population that can respond well to certain drugs and a population that has a higher risk of adverse drug reactions. Implementation of individual treatment can optimize treatment in patients because the dose of treatment and therapeutic options have been adjusted based on individual genetic characteristics.
References
King C, McKenna A, Farzan N, Vijverberg SJ, van der Schee MP, Maitland-van der Zee AH, et al. Pharmacogenomic associations of adverse drug reactions in asthma: systematic review and research prioritization. Pharmacogenomics J 2020; 20(5):621-8.
https://doi.org/10.1038/s41397-019-0140-y
Mommers M, Gielkens-Sijstermans C, Swaen GMH, van Schayck CP. Trends in the prevalence of respiratory symptoms and treatment in Dutch children over a 12 year period: results of the fourth consecutive survey. Thorax 2005; 60(2):97-9.
https://doi.org/10.1136/thx.2004.024786
van Aalderen WM. Childhood asthma: diagnosis and treatment. Scientifica 2012; 2012:674204.
https://doi.org/10.6064/2012/674204
Saglani S, Payne DN, Zhu J, Wang Z, Nicholson AG, Bush A, et al. Early detection of airway wall remodeling and eosinophilic inflammation in preschool wheezers. Am J Respir Crit Care Med 2007; 176(9):858-64.
https://doi.org/10.1164/rccm.200702-212OC
Guilbert TW, Bacharier LB, Fitzpatrick AM. Severe asthma in children. J Allergy Clin Immunol Pract 2014; 2(5):489-500.
https://doi.org/10.1016/j.jaip.2014.06.022
Tse SM, Tantisira K, Weiss ST. The pharmacogenetics and pharmacogenomics of asthma therapy. Pharmacogenomics J 2011; 11(6):383-92.
https://doi.org/10.1038/tpj.2011.46
Bose-Brill S, Xing J, Barnette DJ, Hanks C. Pharmacogenomic testing: aiding in the management of psychotropic therapy for adolescents with autism spectrum disorders. Pharmacogenomics Pers Med 2017; 10:247-52.
https://doi.org/10.2147/PGPM.S130247
Bernsen EC, Hagleitner MM, Kouwenberg TW, Hanff LM. Pharmacogenomics as a tool to limit acute and long-term adverse effects of chemotherapeutics: an update in pediatric oncology. Front Pharmacol 2020; 11:1184.
https://doi.org/10.3389/fphar.2020.01184
Haga SB. Pharmacogenomic testing in pediatrics: navigating the ethical, social, and legal challenges. Pharmacogenomics Pers Med 2019; 12:273-85.
https://doi.org/10.2147/PGPM.S179172
Ross CJD, Visscher H, Rassekh SR, Castro-Pastrana LI, Shereck E, Carleton B, et al. Pharmacogenomics of serious adverse drug reactions in pediatric oncology. J Popul Ther Clin Pharmacol 2011; 18:e134-51.
Maagdenberg H, Vijverberg SJH, Bierings MB, Carleton BC, Arets HGM, de Boer A, et al. Pharmacogenomics in pediatric patients: towards personalized medicine. Pediatr Drugs 2016; 18(4):251-60.
https://doi.org/10.1007/s40272-016-0176-2
Cho SH. Pharmacogenomic approaches to asthma treatment. Allergy Asthma Immunol Res 2010; 2(3):177-82.
https://doi.org/10.4168/aair.2010.2.3.177
Belle DJ, Singh H. Genetic factors in drug metabolism. Am Fam Physician 2008; 77(11):1553-60.
Carleton B, Poole RI, Smith M, Leeder J, Ghannadan R, Ross C, et al. Adverse drug reaction active surveillance: developing a national network in Canada’s children’s hospitals. Pharmacoepidemiol Drug Safety 2009; 18(8):713-21.
https://doi.org/10.1002/pds.1772
Fleming L, Murray C, Bansal AT, Hashimoto S, Bisgaard H, Bush A, et al. The burden of severe asthma in childhood and adolescence: results from the paediatric U-BIOPRED cohorts. Eur Respir J 2015; 46(5):1322-33.
https://doi.org/10.1183/13993003.00780-2015
Park HW, Dahlin A, Tse S, Duan QL, Schuemann B, Martinez FD, et al. Genetic predictors associated with improvement of asthma symptoms in response to inhaled corticosteroids. J Allergy Clin Immunol 133(3):664-9.e5.
https://doi.org/10.1016/j.jaci.2013.12.1042
Tantisira KG, Damask A, Szefler SJ, Schuemann B, Markezich A, Su J, et al. Genome-wide association identifies the t gene as a novel asthma pharmacogenetic locus. Am J Respir Crit Care Med 2012; 185(12):1286-91.
https://doi.org/10.1164/rccm.201111-2061OC
Welter D, MacArthur J, Morales J, Burdett T, Hall P, Junkins H, et al. The NHGRI GWAS Catalog, a curated resource of SNP-trait associations. Nucleic Acids Res 2014; 42:D1001-6.
https://doi.org/10.1093/nar/gkt1229
Adamson PC, Blaney SM. New approaches to drug development in pediatric oncology. Cancer J 2005; 11(4):324-30.
https://doi.org/10.1097/00130404-200507000-00008
Husain A, Loehle JA, Hein DW. Clinical pharmacogenetics in pediatric patients. Pharmacogenomics 2007; 8(10):1403-11.
https://doi.org/10.2217/14622416.8.10.1403
Hall IP. Pharmacogenetics of asthma. Chest 2006; 130(6):1873-8.
https://doi.org/10.1378/chest.130.6.1873
Awasthi S, Gupta S. Pharmacogenomics of pediatric asthma. Indian J Hum Genet 2010; 16(3):111-8.
https://doi.org/10.4103/0971-6866.73398
Turner S, Francis B, Vijverberg S, Pino-Yanes M, van der Zee AHM, Basu K, et al. Childhood asthma exacerbations and the Arg16 β2-receptor polymorphism: a meta-analysis stratified by treatment. J Allergy Clin Immunol 138(1):107-13.e5.
https://doi.org/10.1016/j.jaci.2015.10.045
Vijverberg SJH, Farzan N, Slob EMA, Neerincx AH, van der Zee AHM. Treatment response heterogeneity in asthma: the role of genetic variation. Expert Rev Respir Med 2018; 12(1):55-65.
https://doi.org/10.1080/17476348.2018.1403318
Salah KM, Shafie MMA, Gaber OA, Awad MT. Association between glucocorticosteroid receptors (NR3C1) gene polymorphism and bronchial asthma in children. Zagazig University Medical Journal 2020; 26(1):123-31.
https://doi.org/10.21608/zumj.2019.11975.1204
Perez-Garcia J, Espuela-Ortiz A, Lorenzo-Diaz F, Pino-Yanes M. Pharmacogenetics of pediatric asthma: current perspectives. Pharmacogenomics Pers Med 2020; 13:89-103.
https://doi.org/10.2147/PGPM.S201276
Szalai C, Ungvári I, Pelyhe L, Tölgyesi G, Falus A. Asthma from a pharmacogenomic point of view. Br J Pharmacol 2008; 153(8):1602-14.
https://doi.org/10.1038/bjp.2008.55
Tantisira KG, Hwang ES, Raby BA, Silverman ES, Lake SL, Richter BG, et al. TBX21: A functional variant predicts improvement in asthma with the use of inhaled corticosteroids. Proc Natl Acad Sci USA 2004; 101(52):18099-104.
https://doi.org/10.1073/pnas.0408532102
Pahl A, Benediktus E, Chialda L. Pharmacogenomics of asthma. Curr Pharm Des 2006; 12(25):3195-3206.
https://doi.org/10.2174/138161206778194105
Sampson AP, Siddiqui S, Buchanan D, Howarth PH, Holgate ST, Holloway JW, et al. Variant LTC4 synthase allele modifies cysteinyl leukotriene synthesis in eosinophils and predicts clinical response to zafirlukast. Thorax 2000; 55(Suppl 2):28-31.
https://doi.org/10.1136/thorax.55.suppl_2.s28
Asano K, Shiomi T, Hasegawa N, Nakamura H, Kudo H, Matsuzaki T, et al. Leukotriene C4 synthase gene A(-444)C polymorphism and clinical response to a CYS-LT1 antagonist, pranlukast, in Japanese patients with moderate asthma. Pharmacogenetics 2002; 12(7):565-70.
https://doi.org/10.1097/00008571-200210000-00009
Keskin O, Uluca Ü, Birben E, Coşkun Y, Ozkars MY, Keskin M, et al. Genetic associations of the response to inhaled corticosteroids in children during an asthma exacerbation. Pediatr Allergy Immunol 2016; 27(5):507-13.
https://doi.org/10.1111/pai.12566
Tantisira KG, Litonjua AA, Sylvia J, Martinez FD, Lazarus SC, Nakamura, Y, et al. Genomewide association between GLCCI1 and response to glucocorticoid therapy in asthma. N Engl J Med 2011; 365(13):1173-83.
https://doi.org/10.1056/NEJMoa0911353
Hosking L, Bleecker E, Ghosh S, Yeo A, Jacques L, Mosteller M, et al. GLCCI1 rs37973 does not influence treatment response to inhaled corticosteroids in white subjects with asthma. J Allergy Clin Immunol 2014; 133(2):587-9.
https://doi.org/10.1016/j.jaci.2013.08.024
Koster ES, van der Zee AHM, Tavendale R, Mukhopadhyay S, Vijverberg SJH, Raaijmakers JAM, et al. FCER2 T2206C variant associated with chronic symptoms and exacerbations in steroid-treated asthmatic children: FCER2 T2206C variant associated with chronic symptoms and exacerbations. Allergy 2011; 66(12):1546-52.
https://doi.org/10.1111/j.1398-9995.2011.02701.x
Berce V, Kozmus CEP, Potočnik U. Association among ORMDL3 gene expression, 17q21 polymorphism and response to treatment with inhaled corticosteroids in children with asthma. Pharmacogenomics J 2013; 13(6):523-9.
https://doi.org/10.1038/tpj.2012.36
Balantic M, Rijavec M, Kavalar MS, Suskovic S, Silar M, Kosnik M, et al. Asthma treatment outcome in children is associated with vascular endothelial growth factor A (VEGFA) polymorphisms. Mol Diagn Ther 2012; 16(3):173-80.
https://doi.org/10.1007/BF03262206
Mougey E, Lang JE, Allayee H, Teague WG, Dozor AJ, Wise RA, et al. ALOX5 polymorphism associates with increased leukotriene production and reduced lung function and asthma control in children with poorly controlled asthma. Clin Exp Allergy 2013; 43(5):512-20.
https://doi.org/10.1111/cea.12076
Tcheurekdjian H, Via M, Giacomo AD, Corvol H, Eng C, Thyne S, et al. ALOX5AP and LTA4H polymorphisms modify augmentation of bronchodilator responsiveness by leukotriene modifiers in Latinos. J Allergy Clin Immunol 2010; 126(4):853-8.
https://doi.org/10.1016/j.jaci.2010.06.048
Mougey EB, Lang JE, Wen X, Lima JJ. Effect of citrus juice and SLCO2B1 genotype on the pharmacokinetics of montelukast. J Clin Pharmacol Trial 2011; 51(5):751-60.
https://doi.org/10.1177/0091270010374472
Bleecker ER, Nelson HS, Kraft M, Corren J, Meyers DA, Yancey SW, et al. β2 -receptor polymorphisms in patients receiving salmeterol with or without fluticasone propionate. Am J Respir Crit Care Med 2010; 181(7):676-87.
https://doi.org/10.1164/200809-1511OC
Drake KA, Torgerson DG, Gignoux CR, Galanter JM, Roth LA, Huntsman S, et al. A genome-wide association study of bronchodilator response in Latinos implicates rare variants. J Allergy Clin Immunol 2014; 133(2):370-8.
https://doi.org/10.1016/j.jaci.2013.06.043
Duan QL, Du R, Lasky-Su J, Klanderman BJ, Partch AB, Peters SP, et al. A polymorphism in the thyroid hormone receptor gene is associated with bronchodilator response in asthmatics. Pharmacogenomics J 2013; 13(2):130-6.
https://doi.org/10.1038/tpj.2011.56
de Beaumais TA, Jacqz-Aigrain E. Pharmacogenetics: applications to pediatric patients. Adv Pharmacol 2018; 83:191-215.
https://doi.org/10.1016/bs.apha.2018.04.006
Dahlin A, Litonjua A, Lima JJ, Tamari M, Kubo M, Irvin CG, et al. Genome-wide association study identifies novel pharmacogenomic loci for therapeutic response to montelukast in asthma. PLoS One 2015; 10(6):e0129385.
https://doi.org/10.1371/journal.pone.0129385
Kersten ETG, Koppelman GH. Pharmacogenetics of asthma: toward precision medicine. Curr Opin Pulm Med 2017; 23(1):12-20.