Pharmacogenomics and Pediatric Asthmatic Medications
Abstract
:1. Introduction
2. Beta-2 Agonists
2.1. SABA and ADRB2 Variations
2.2. SABA and Other Gene Variations
2.3. LABA with or without ICS and ADRB2 Variations
3. Inhaled Corticosteroids (ICS)
4. Leukotriene Modifiers (LTM)
4.1. Genes That Affect Montelukast Response
4.2. Genes Affecting Other Leukotriene Modifier Responses
5. Conclusions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Centers for Disease Control and Prevention. 2019 National Health Interview Survey (NHIS) Data. Available online: https://www.cdc.gov/asthma/nhis/2019/data.htm/ (accessed on 25 October 2021).
- Weiss, S.T.; Litonjua, A.A.; Lange, C.; Lazarus, R.; Liggett, S.B.; Bleecker, E.R.; Tantisira, K.G. Overview of the pharmacogenetics of asthma treatment. Pharmacogenomics 2006, 6, 311–326. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- The Global Asthma Report 2018; Global Asthma Network: Auckland, New Zealand. 2018. Available online: globalasthmareport.org (accessed on 31 January 2022).
- Nurmagambetov, T.; Kuwahara, R.; Garbe, P. The Economic Burden of Asthma in the United States 2008-2013. Ann. Am. Thorac Soc. 2018, 15, 348–356. [Google Scholar] [CrossRef] [PubMed]
- Centers for Disease Control and Prevention. Asthma-Related Missed School Days among Children Aged 5–17 Years. Available online: https://www.cdc.gov/asthma/asthma_stats/missing_days.htm/ (accessed on 20 August 2021).
- Dharmage, S.C.; Perret, J.L.; Custovic, A. Epidemiology of Asthma in Children and Adults. Front Pediatr. 2019, 18, 246. [Google Scholar] [CrossRef] [PubMed]
- Global Initiative for Asthma. Global Initiative for Asthma—GINA. Available online: https://ginasthma.org/ (accessed on 2 September 2021).
- Gustafsson, P.M.; Watson, L.; Davis, K.J.; Rabe, K.F. Poor asthma control in children: Evidence from epidemiological surveys and implications for clinical practice. Int. J. Clin. Pract. 2006, 60, 321–334. [Google Scholar] [CrossRef] [PubMed]
- Gallagher, R.M.; Mason, J.R.; Bird, K.A.; Kirkham, J.J.; Peak, M.; Williamson, P.R.; Nunn, A.J.; Turner, M.A.; Pirmohamed, M.; Smyth, R.L. Adverse drug reactions causing admission to a paediatric hospital. PLoS ONE 2012, 7, e50127. [Google Scholar] [CrossRef] [Green Version]
- Clancy, J.P.; Johnson, S.G.; Yee, S.W.; McDonagh, E.M.; Caudle, K.E.; Klein, T.E.; Cannavo, M.; Giacomini, K.M. Clinical Pharmacogenetics Implementation Consortium. Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for ivacaftor therapy in the context of CFTR genotype. Clin. Pharmacol. Ther. 2014, 95, 592–597. [Google Scholar] [CrossRef] [Green Version]
- Billington, C.K.; Penn, R.B.; Hall, I.P. β2 Agonists. Handb. Exp. Pharmacol. 2017, 237, 23–40. [Google Scholar]
- Carroll, C.L.; Stoltz, P.; Schramm, C.M.; Zucker, A.M. B2-adrenergic receptor polymorphisms affect response to treatment in children with severe asthma exacerbations. Chest 2009, 135, 1186–1192. [Google Scholar] [CrossRef]
- Ortega, V.E.; Meyers, D.A.; Bleecker, E.R. Asthma pharmacogenetics and the development of genetic profiles for personalized medicine. Pharmgenom. Pers. Med. 2015, 8, 9–22. [Google Scholar]
- Choudhry, S.; Ung, N.; Avila, P.C.; Ziv, E.; Nazario, S.; Casal, J.; Torres, A.; Gorman, J.D.; Salari, K.; Rodriguez-Santana, J.R.; et al. Pharmacogenetic differences in response to albuterol between Puerto Ricans and Mexicans with asthma. Am. J. Respir. Crit. Care. Med. 2005, 171, 563–570. [Google Scholar] [CrossRef] [Green Version]
- Finkelstein, Y.; Bournissen, F.G.; Hutson, J.R.; Shannon, M. Polymorphism of the ADRB2 gene and response to inhaled beta- agonists in children with asthma: A meta-analysis. J. Asthma 2009, 46, 900–905. [Google Scholar] [CrossRef] [PubMed]
- Lima, J.J.; Thomason, D.B.; Mohamed, M.H.; Eberle, L.V.; Self, T.H.; Johnson, J.A. Impact of genetic polymorphisms of the beta2-adrenergic receptor on albuterol bronchodilator pharmacodynamics. Clin. Pharmacol. Ther. 1999, 65, 519–525. [Google Scholar] [CrossRef]
- Martinez, F.D.; Graves, P.E.; Baldini, M.; Solomon, S.; Erickson, R. 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, 3184–3188. [Google Scholar] [CrossRef] [PubMed]
- Scaparrotta, A.; Franzago, M.; Marcovecchio, M.L.; Di Pillo, S.; Chiarelli, F.; Mohn, A.; Stuppia, L. Role of THRB, ARG1, and ADRB2 Genetic Variants on Bronchodilators Response in Asthmatic Children. J. Aerosol. Med. Pulm. Drug Deliv. 2019, 32, 164–173. [Google Scholar] [CrossRef]
- Salah, K.; Morsy, S.; Atta, A. Effects of β2-adrenergic receptor polymorphisms on asthma severity and response to salbutamol in Egyptian children. Egypt J. Pediatr. Allergy Immunol. 2012, 10, 81–86. [Google Scholar]
- Israel, E.; Chinchilli, V.M.; Ford, J.G.; Boushey, H.A.; Cherniack, R.; Craig, T.J.; Deykin, A.; Fagan, J.K.; Fahy, J.V.; Fish, J.; et al. Use of regularly scheduled albuterol treatment in asthma: Genotype-stratified, randomised, placebo-controlled cross-over trial. Lancet 2004, 364, 1505–1512. [Google Scholar] [CrossRef]
- Turner, S.W. Genetic predictors of response to therapy in childhood asthma. Mol. Diagn. Ther. 2009, 13, 127–135. [Google Scholar] [CrossRef]
- Giubergia, V.; Gravina, L.P.; Castanos, C.; Chertkoff, L.; Grenoville, M. Influence of beta2-adrenoceptor polymorphisms on the response to chronic use of albuterol in asthmatic children. Pediatr. Pulmonol. 2008, 43, 421–425. [Google Scholar] [CrossRef]
- Jovicic, N.; Babic, T.; Dragicevic, S.; Nestorovic, B.; Nikolic, A. ADRB2 gene polymorphisms and salbutamol responsiveness in Serbian children with asthma. Balk. J. Med. Genet. 2018, 21, 33–38. [Google Scholar] [CrossRef] [Green Version]
- Perez-Garcia, J.; Espuela-Ortiz, A.; Lorenzo-Diaz, F.; Pino-Yanes, M. Pharmacogenetics of Pediatric Asthma: Current Perspectives. Pharmgenom. Pers. Med. 2020, 13, 89–103. [Google Scholar] [CrossRef] [Green Version]
- Hikino, K.; Kobayashi, S.; Ota, E.; Mushiroda, T.; Urayama, K.Y.; Kobayashi, T. A meta-analysis of the influence of ADRB2 genetic polymorphisms on albuterol (salbutamol) therapy in patients with asthma. Br. J. Clin. Pharmacol. 2021, 87, 1708–1716. [Google Scholar] [CrossRef] [PubMed]
- Alghobashy, A.A.; Elsharawy, S.A.; Alkholy, U.M.; Abdalmonem, N.; Abdou, M.A.; Basset, M.A.A.; Pasha, H.F. B2 adrenergic receptor gene polymorphism effect on childhood asthma severity and response to treatment. Pediatr. Res. 2018, 83, 597–605. [Google Scholar] [CrossRef]
- Elbahlawan, L.; Binaei, S.; Christensen, M.L.; Zhang, Q.; Quasney, M.W.; Dahmer, M.K. β2-Adrenergic receptor polymorphisms in African American children with status asthmaticus. Pediatr. Crit. Care Med. 2006, 7, 15–18. [Google Scholar] [CrossRef]
- The Childhood Asthma Management Program (CAMP): Design, rationale, and methods. Control Clin. Trials. 1999, 20, 91–120. [CrossRef]
- Peters, S.P.; Anthonisen, N.; Castro, M.; Holbrook, J.T.; Irvin, C.G.; Smith, L.J.; Wise, R.A. Randomized comparison of strategies for reducing treatment in mild persistent asthma. N. Engl. J. Med. 2007, 356, 2027–2039. [Google Scholar] [PubMed]
- American Lung Association Asthma Clinical Research Centers. Clinical trial of low-dose theophylline and montelukast in patients with poorly controlled asthma. Am. J. Respir. Crit. Care Med. 2007, 175, 235–242. [Google Scholar] [CrossRef] [PubMed]
- Litonjua, A.A.; Lasky-Su, J.; Schneiter, K.; Tantisira, K.G.; Lazarus, R.; Klanderman, B.; Lima, J.J.; Irvin, C.G.; Peters, S.P.; Hanrahan, J.P.; et al. ARG1 is a novel bronchodilator response gene: Screening and replication in four asthma cohorts. Am. J. Respir. Crit. Care Med. 2008, 178, 688–694. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Duan, Q.L.; Du, R.; Lasky-Su, J.; Klanderman, B.J.; Partch, A.B.; Peters, S.P.; Irvin, C.G.; Hanrahan, J.P.; Lima, J.J.; Blake, K.V.; et al. A polymorphism in the thyroid hormone receptor gene is associated with bronchodilator response in asthmatics. Pharm. J. 2013, 13, 130–136. [Google Scholar] [CrossRef]
- Duan, Q.L.; Lasky-Su, J.; Himes, B.E.; Qiu, W.; Litonjua, A.A.; Damask, A.; Lazarus, R.; Klanderman, B.; Irvin, C.G.; Peters, S.P.; et al. A genome-wide association study of bronchodilator response in asthmatics. Pharm. J. 2014, 14, 41–47. [Google Scholar] [CrossRef] [Green Version]
- Padhukasahasram, B.; Yang, J.J.; Levin, A.M.; Yang, M.; Burchard, E.G.; Kumar, R.; Kwok, P.Y.; Seibold, M.A.; Lanfear, D.E.; Williams, L.K. Gene-based association identifies SPATA13-AS1 as a pharmacogenomic predictor of inhaled short-acting beta-agonist response in multiple population groups. Pharm. J. 2014, 14, 365–371. [Google Scholar] [CrossRef] [Green Version]
- Himes, B.E.; Jiang, X.; Hu, R.; Wu, A.C.; Lasky-Su, J.A.; Klanderman, B.J.; Ziniti, J.; Senter-Sylvia, J.; Lima, J.J.; Irvin, C.G.; et al. Genome-wide association analysis in asthma subjects identifies SPATS2L as a novel bronchodilator response gene. PLoS Genet. 2012, 8, e1002824. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Israel, E.; Lasky-Su, J.; Markezich, A.; Damask, A.; Szefler, S.J.; Schuemann, B.; Klanderman, B.; Sylvia, J.; Kazani, S.; Wu, R.; et al. Genome-wide association study of short-acting β2-agonists. A novel genome-wide significant locus on chromosome 2 near ASB3. Am. J. Respir. Crit. Care Med. 2015, 191, 530–537. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Poon, A.H.; Tantisira, K.G.; Litonjua, A.A.; Lazarus, R.; Xu, J.; Lasky-Su, J.; Lima, J.J.; Irvin, C.G.; Hanrahan, J.P.; Lange, C.; et al. Association of corticotropin-releasing hormone receptor-2 genetic variants with acute bronchodilator response in asthma. Pharmacogenet. Genom. 2008, 18, 373–382. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Spear, M.L.; Hu, D.; Pino-Yanes, M.; Huntsman, S.; Eng, C.; Levin, A.M.; Ortega, V.E.; White, M.J.; McGarry, M.E.; Thakur, N.; et al. A genome-wide association and admixture mapping study of bronchodilator drug response in African Americans with asthma. Pharm. J. 2019, 19, 249–259. [Google Scholar] [CrossRef] [PubMed]
- Bleecker, E.R.; Nelson, H.S.; Kraft, M.; Corren, J.; Meyers, D.A.; Yancey, S.W.; Anderson, W.H.; Emmett, A.H.; Ortega, H.G. Beta2-receptor polymorphisms in patients receiving salmeterol with or without fluticasone propionate. Am. J. Respir. Crit. Care Med. 2010, 181, 676–687. [Google Scholar] [CrossRef] [PubMed]
- Bleecker, E.R.; Postma, D.S.; Lawrance, R.M.; Meyers, D.A.; Ambrose, H.J.; Goldman, M. Effect of ADRB2 polymorphisms on response to long-acting b2-agonist therapy: A pharmacogenetic analysis of two randomised studies. Lancet 2007, 370, 2118–2125. [Google Scholar] [CrossRef]
- Bleecker, E.R.; Yancey, S.W.; Baitinger, L.A.; Edwards, L.D.; Klotsman, M.; Anderson, W.H.; Dorinsky, P.M. Salmeterol response is not affected by beta2-adrenergic receptor genotype in subjects with persistent asthma. J. Allergy Clin. Immunol. 2006, 118, 809–816. [Google Scholar] [CrossRef]
- Giubergia, V.; Gravina, L.; Castanos, C.; Chertkoff, L. Influence of beta(2)-adrenergic receptor polymorphisms on asthma exacerbation in children with severe asthma regularly receiving salmeterol. Ann. Allergy Asthma Immunol. 2013, 110, 156–160. [Google Scholar] [CrossRef]
- Wang, X.; Li, Q.; Liu, R.; He, J.; Wu, D.; Wang, Y.; Zhang, J. ADRB2 Arg16Gly polymorphism and pulmonary function response of inhaled corticosteroids plus long-acting beta agonists for asthma treatment: A systematic review and meta-analysis. Can. Respir. J. 2018, 5712805. [Google Scholar] [CrossRef] [Green Version]
- Palmer, C.N.; Lipworth, B.J.; Lee, S.; Ismail, T.; Macgregor, D.F.; Mukhopadhyay, S. Arginine-16 beta2 adrenoceptor genotype predisposes to exacerbations in young asthmatics taking regular salmeterol. Thorax 2006, 61, 940–944. [Google Scholar] [CrossRef] [Green Version]
- Zuurhout, M.J.; Vijverberg, S.J.; Raaijmakers, J.A.; Koenderman, L.; Postma, D.S.; Koppelman, G.H.; Maitland-van der Zee, A.H. 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, 1965–1971. [Google Scholar] [CrossRef] [PubMed]
- Wechsler, M.E.; Lehman, E.; Lazarus, S.C.; Lemanske, R.F.; Boushey, H.A., Jr.; Deykin, A.; Fahy, J.V.; Sorkness, C.A.; Chinchilli, V.M.; Craig, T.J.; et al. Beta-Adrenergic receptor polymorphisms and response to salmeterol. Am. J. Respir. Crit. Care Med. 2006, 173, 519–526. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lipworth, B.J.; Basu, K.; Donald, H.P.; Tavendale, R.; Macgregor, D.F.; Ogston, S.A.; Palmer, C.N.; Mukhopadhyay, S. Tailored second-line therapy in asthmatic children with the Arg(16) genotype. Clin. Sci. (Lond.). 2013, 124, 521–528. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Basu, K.; Palmer, C.N.; Tavendale, R.; Lipworth, B.J.; Mukhopadhyay, S. Adrenergic beta2- receptor genotype predisposes to exacerbations in steroid-treated asthmatic patients taking frequent albuterol or salmeterol. J. Allergy Clin. Immunol. 2009, 124, 1188–1194.e3. [Google Scholar] [CrossRef]
- Turner, S.; Francis, B.; Vijverberg, S.; Pino-Yanes, M.; Maitland-van der Zee, A.H.; Basu, K.; Bignell, L.; Mukhopadhyay, S.; Tavendale, R.; Palmer, C.; et al. Pharmacogenomics in Childhood Asthma Consortium. Childhood asthma exacerbations and the Arg16 β2-receptor polymorphism: A meta-analysis stratified by treatment. J Allergy Clin. Immunol. 2016, 138, 107–113.e5. [Google Scholar] [CrossRef] [Green Version]
- Barnes, P.J. Inhaled Corticosteroids. Pharmaceuticals 2010, 3, 514–540. [Google Scholar] [CrossRef] [Green Version]
- Tantisira, K.G.; Lasky-Su, J.; Harada, M.; Murphy, A.; Litonjua, A.A.; Himes, B.E.; Lange, C.; Lazarus, R.; Sylvia, J.; Klanderman, B.; et al. Genomewide association between GLCCI1 and response to glucocorticoid therapy in asthma. N. Engl. J. Med. 2011, 365, 1173–1183. [Google Scholar] [CrossRef] [Green Version]
- Thompson, B.; Hawcutt, D.; Carr, D.; Jorgensen, A.; Smyth, R.; Pirmohamed, M. S31 variation at GLC1CI1: Association with increased steroid dose but not adrenal suppression in asthmatic children. Thorax 2012, 67 (Suppl. 2), A17. [Google Scholar] [CrossRef] [Green Version]
- Vijverberg, S.J.; Tavendale, R.; Leusink, M.; Koenderman, L.; Raaijmakers, J.A.; Postma, D.S.; Koppelman, G.H.; Turner, S.W.; Mukhopadhyay, S.; Palmer, C.N.; et al. Pharmacogenetic analysis of GLCCI1 in three north European pediatric asthma populations with a reported use of inhaled corticosteroids. Pharmacogenomics 2014, 15, 799–806. [Google Scholar] [CrossRef]
- Huang, J.; Hu, X.; Zheng, X.; Kuang, J.; Liu, C.; Wang, X.; Tang, Y. Effects of STIP1 and GLCCI1 polymorphisms on the risk of childhood asthma and inhaled corticosteroid response in Chinese asthmatic children. BMC Pulm. Med. 2020, 20, 303. [Google Scholar] [CrossRef]
- Kim, M.H.; Kim, S.H.; Kim, Y.K.; Hong, S.J.; Min, K.U.; Cho, S.H.; Park, H.W. A polymorphism in the histone deacetylase 1 gene is associated with the response to corticosteroids in asthmatics. Korean J. Intern. Med. 2013, 28, 708–714. [Google Scholar] [CrossRef] [PubMed]
- Tantisira, K.G.; Lake, S.; Silverman, E.S.; Palmer, L.J.; Lazarus, R.; Silverman, E.K.; Liggett, S.B.; Gelfand, E.W.; Rosenwasser, L.J.; Richter, B.; et al. Corticosteroid pharmacogenetics: Association of sequence variants in CRHR1 with improved lung function in asthmatics treated with inhaled corticosteroids. Hum. Mol. Genet. 2004, 13, 1353–1359. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tantisira, K.G.; Hwang, E.S.; Raby, B.A.; Silverman, E.S.; Lake, S.L.; Richter, B.G.; Peng, S.L.; Drazen, J.M.; Glimcher, L.H.; Weiss, S.T. TBX21: A functional variant predicts improvement in asthma with the use of inhaled corticosteroids. Proc. Natl. Acad. Sci. USA 2004, 101, 18099–18104. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tantisira, K.G.; Silverman, E.S.; Mariani, T.J.; Xu, J.; Richter, B.G.; Klanderman, B.J.; Litonjua, A.A.; Lazarus, R.; Rosenwasser, L.J.; Fuhlbrigge, A.L.; et al. FCER2: A pharmacogenetic basis for severe exacerbations in children with asthma. J. Allergy. Clin. Immunol. 2007, 120, 1285–1291. [Google Scholar] [CrossRef]
- Koster, E.S.; Maitland-van der Zee, A.H.; Tavendale, R.; Mukhopadhyay, S.; Vijverberg, S.J.; Raaijmakers, J.A.; Palmer, C.N. FCER2 T2206C variant associated with chronic symptoms and exacerbations in steroid-treated asthmatic children. Allergy 2011, 66, 1546–1552. [Google Scholar] [CrossRef]
- Keskin, O.; Uluca, Ü.; Birben, E.; Coşkun, Y.; Ozkars, M.Y.; Keskin, M.; Kucukosmanoglu, E.; Kalayci, O. Genetic associations of the response to inhaled corticosteroids in children during an asthma exacerbation. Pediatr. Allergy Immunol. 2016, 27, 507–513. [Google Scholar] [CrossRef]
- Stockmann, C.; Fassl, B.; Gaedigk, R.; Nkoy, F.; Uchida, D.A.; Monson, S.; Reilly, C.A.; Leeder, J.S.; Yost, G.S.; Ward, R.M. Fluticasone propionate pharmacogenetics: CYP3A4*22 polymorphism and pediatric asthma control. J. Pediatr. 2013, 162, 1227–1227, 1227.e1–2. [Google Scholar] [CrossRef] [Green Version]
- Stockmann, C.; Reilly, C.A.; Fassl, B.; Gaedigk, R.; Nkoy, F.; Stone, B.; Roberts, J.K.; Uchida, D.A.; Leeder, J.S.; Sherwin, C.M.; et al. Effect of CYP3A5*3 on asthma control among children treated with inhaled beclomethasone. J. Allergy Clin. Immunol. 2015, 136, 505–507. [Google Scholar] [CrossRef] [Green Version]
- Lima, J.J. Treatment heterogeneity in asthma: Genetics of response to leukotriene modifiers. Mol. Diagn. Ther. 2007, 11, 97–104. [Google Scholar] [CrossRef]
- Choi, J. Leukotriene Receptor Antagonists. Available online: https://www.ncbi.nlm.nih.gov/books/NBK554445/ (accessed on 5 November 2021).
- Drazen, J.M.; Israel, E.; O’Byrne, P.M. Treatment of asthma with drugs modifying the leukotriene pathway. N. Engl. J. Med. 1999, 340, 197–206. [Google Scholar] [CrossRef]
- Bäck, M. Functional characteristics of cysteinyl-leukotriene receptor subtypes. Life Sci. 2002, 71, 611–622. [Google Scholar] [CrossRef]
- Kim, J.H.; Lee, S.Y.; Kim, H.B.; Jin, H.S.; Yu, J.H.; Kim, B.J.; Kim, B.S.; Kang, M.J.; Jang, S.O.; Hong, S.J. TBXA2R gene polymorphism and responsiveness to leukotriene receptor antagonist in children with asthma. Clin. Exp. Allergy 2008, 38, 51–59. [Google Scholar] [CrossRef]
- Mougey, E.; Lang, J.E.; Allayee, H.; Teague, W.G.; Dozor, A.J.; Wise, R.A.; Lima, J.J. 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, 512–520. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Klotsman, M.; York, T.P.; Pillai, S.G.; Vargas-Irwin, C.; Sharma, S.S.; van den Oord, E.J.; Anderson, W.H. Pharmacogenetics of the 5-lipoxygenase biosynthetic pathway and variable clinical response to montelukast. Pharmacogenet. Genom. 2007, 17, 189–196. [Google Scholar] [CrossRef]
- Telleria, J.J.; Blanco-Quiros, A.; Varillas, D.; Armentia, A.; Fernandez-Carvajal, I.; Jesus Alonso, M.; Diez, I. ALOX5 promoter genotype and response to montelukast in moderate persistent asthma. Respir. Med. 2008, 102, 857–861. [Google Scholar] [CrossRef] [PubMed]
- Kang, M.J.; Kwon, J.W.; Kim, B.J.; Yu, J.; Choi, W.A.; Shin, Y.J.; Hong, S.J. Polymorphisms of the PTGDR and LTC4S influence responsiveness to leukotriene receptor antagonists in Korean children with asthma. J. Hum. Genet. 2011, 56, 284–289. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lee, S.Y.; Kim, H.B.; Kim, J.H.; Kim, B.S.; Kang, M.J.; Jang, S.O.; Seo, H.J.; Hong, S.J. Responsiveness to montelukast is associated with bronchial hyperresponsiveness and total immunoglobulin E but not polymorphisms in the leukotriene C4 synthase and cysteinyl leukotriene receptor 1 genes in Korean children with exercise-induced asthma (EIA). Clin. Exp. Allergy 2007, 37, 1487–1493. [Google Scholar] [CrossRef]
- Whelan, G.J.; Blake, K.; Kissoon, N.; Duckworth, L.J.; Wang, J.; Sylvester, J.E.; Lima, J.J. Effect of montelukast on time-course of exhaled nitric oxide in asthma: Influence of LTC4 synthase A(-444)C polymorphism. Pediatr Pulmonol. 2003, 36, 413–420. [Google Scholar] [CrossRef]
- Mougey, E.B.; Feng, H.; Castro, M.; Irvin, C.G.; Lima, J.J. Absorption of montelukast is transporter mediated: A common variant of OATP2B1 is associated with reduced plasma concentrations and poor response. Pharmacogenet. Genom. 2009, 19, 129–138. [Google Scholar] [CrossRef] [Green Version]
- Li, Q.; Wang, K.; Shi, H.Y.; Wu, Y.E.; Zhou, Y.; Kan, M.; Zheng, Y.; Hao, G.X.; Yang, X.M.; Yang, Y.L. Developmental Pharmacogenetics of SLCO2B1 on Montelukast Pharmacokinetics in Chinese Children. Drug Des. Devel. Ther. 2019, 13, 4405–4411. [Google Scholar] [CrossRef] [Green Version]
- Karonen, T.; Neuvonen, P.J.; Backman, J.T. CYP2C8 but not CYP3A4 is important in the pharmacokinetics of montelukast. Br. J. Clin. Pharmacol. 2012, 73, 257–267. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Aquilante, C.L.; Niemi, M.; Gong, L.; Altman, R.B.; Klein, T.E. PharmGKB summary: Very important pharmacogene information for cytochrome P450, family 2, subfamily C, polypeptide 8. Pharmacogenet. Genom. 2013, 23, 721–728. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bouchette, D.; Preuss, C.V. Zileuton. Available online: https://www.ncbi.nlm.nih.gov/books/NBK448202/ (accessed on 21 August 2021).
- Tcheurekdjian, H.; Via, M.; De Giacomo, A.; Corvol, H.; Eng, C.; Thyne, S.; Chapela, R.; Rodriguez-Cintron, W.; Rodriguez-Santana, J.R.; Avila, P.C.; et al. Genetics of Asthma in Latino Americans Study. Genetics of asthma in Latino Americans study. ALOX5AP and LTA4H polymorphisms modify augmentation of bronchodilator responsiveness by leukotriene modifiers in Latinos. J. Allergy Clin. Immunol. 2010, 126, 853–858. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wu, A.C.; Gay, C.; Rhett, M.D.; Stout, N.; Weiss, S.T.; Fuhlbrigge, A.L. Pharmacogenomic test that predicts response to inhaled corticosteroids in adults with asthma likely to be cost-saving. Pharmacogenomics 2015, 16, 591–600. [Google Scholar] [CrossRef] [Green Version]
- Devonshire, A.L.; Rajesh, K. Pediatric asthma: Principles and treatment. Allergy Asthma Proc. 2019, 40, 389–392. [Google Scholar] [CrossRef]
- Vitale, C.; Maglio, A.; Pelaia, C.; Vatrella, A. Long-term treatment in pediatric asthma: An update on chemical pharmacotherapy. Expert Opin. Pharmacother. 2017, 18, 667–676. [Google Scholar] [CrossRef]
Study | Population | Medication | Measurement | Results |
---|---|---|---|---|
Choudhry [14] | Puerto Ricans and Mexican | Albuterol | % change in predicted post- and pre- bronchodilator FEV1 | Arg16Arg and Arg16Gly showed favorable response compared to Gly16Gly in Puerto Ricans |
Finkelstein [15] | Multiethnic | Albuterol | Positive BDR ≥ 15% FEV1 response | Arg16Arg were more likely to respond than Arg16Gly or Gly16Gly |
Martinez [17] | Hispanic parents or at least one non-Hispanic parent | Albuterol | % change in predicted post- and pre- bronchodilator FEV1 | Arg16Arg and Arg16Gly were more likely to respond than Gly16Gly |
Scaparrotta [18] | European | Fenoterol | Post BD FEV1(%) | Arg16Arg showed favorable response compared to Gly16Gly or Arg16Gly |
Salah [19] | Egyptian | Albuterol | % change in predicted post- and pre- bronchodilator FEV1 | Arg16Arg showed favorable response compared to Gly16Gly and Arg16Gly |
Carroll [21] | Hispanic, African American, White | Albuterol | Positive Clinical outcomes: ICU stay and duration of therapy | Gly16Gly produces more rapid and positive clinical outcomes than Arg genotypes |
Giubergia [22] | Argentina | Albuterol | Change in FEV1 from Day 1 to Day 30 | Arg16Arg showed reduced response |
Jovicic [23] | Serbian | Albuterol | dFEV1 | +46 G alleles (GG, GA) showed favorable response |
Study | Population | Medication | Measurement | Results |
---|---|---|---|---|
Alghobashy [26] | Egyptian | Albuterol or terbutaline | FVC, FEV1, FEV1/FVC ratio | Gln17Glu showed favorable outcomes compared to Glu27Glu |
Giubergia [22] | Argentinean | Albuterol | Change in FEV1 from Day 1 to Day 30 | Glu27Glu showed favorable outcomes compared to Gln27Gln |
Elbahlawan [27] | African American | Terbutaline ± aminophylline | Addition of aminophylline | Gln27Gln has a better response to beta-2 agonists than Glu27Glu |
Study | Population | Gene/Location | Medication | Measurement | Results |
---|---|---|---|---|---|
Litonjua [31] | White | ARG1 | Albuterol | % difference in FEV1 between pre- and post-bronchodilator | rs2781659 AA genotype showed favorable response compared to AG or GG genotypes |
Scaparrotta [18] | Caucasian | ARG1 THRB | Fenoterol | Increase in FEV1 > 12% from baseline | rs2781659 variants in children inconclusive rs892940 variants in children inconclusive |
Duan [32] | White | THRB | Albuterol | % difference in FEV1 pre- and post-bronchodilator | rs892940 A allele showed favorable response over G allele |
Duan [33] | White | VDR and WT1 | Albuterol | % difference in FEV1 pre- and post-bronchodilator | No statistical significance found |
Padhukasahasram [34] | African Americans and Europeans | SPATA13-AS1 | Albuterol | % change in FEV1 pre- and post-bronchodilator | rs9507294, rs912142, rs2248119, rs9551086, and rs9553225 produced favorable response |
Himes [35] | White | SPATS2L | Albuterol | % difference in FEV1 pre- and post-bronchodilator | rs295137 TT produced favorable response compared to CC or TC |
Israel [36] | White | Near ASB3 | Albuterol | % change in FEV1 pre- and post-bronchodilator | rs350729, rs1840321, rs1384918, and rs1319797 homozygous major allele produce favorable response |
Poon [37] | Caucasian | CRHR2 | Albuterol | % change in FEV1 pre- and post-bronchodilator | rs255100A, rs7793837T, and rs2267715G produced favorable response in children but not in adults |
Spear [38] | Multiethnic | Chromosome 9q21 PRKG1 | Albuterol | % change in FEV1 pre- and post-bronchodilator | rs73650726G produced favorable response Findings unsupported in replication |
Study | Population | Medication | Measurement | Results |
---|---|---|---|---|
Bleecker [39] | Multiethnic | Fluticasone ± salmeterol | Change in PEF | At position 16, Arg/Arg, Gly/Gly, and Arg/Gly produce similar response |
Bleecker [40] | Multiethnic | Budesonide + formoterol or Fluticasone + salmeterol | FEV1, PEF | At position 16, Arg/Arg, Gly/Gly, and Arg/Gly produce similar response |
Bleecker [41] | Multiethnic | Fluticasone + salmeterol | FEV1 | Improvement in BDR regardless of genotype |
Guibergia [42] | Argentinean | Fluticasone + salmeterol | FEV1 | No association at position 16 or 27 |
Wang [43] | Multiethnic | Fluticasone + salmeterol | Varies based on study | No association at position 16 |
Palmer [44] | Scotland | ICS + LABA or ICS + LABA + montelukast | Exacerbations (school absences, short course of oral steroids, hospital admissions) | Arg16Arg genotypes are at greater risk.At position 27, no association found |
Zuurhout [45] | Netherlands | ICS or ICS + LABA | Exacerbations (asthma-related hospital visits and oral steroids) | Arg16Arg genotypes are at greater risk in those taking ICS + LABA |
Lipworth [47] | Scotland | Fluticasone + oral montelukast or salmeterol + fluticasone | School absences, FEV1, asthma symptoms | Arg16 variant produced less favorable response with salmeterol |
Basu [48] | Scotland | Albuterol or salmeterol | Exacerbations (school absences, oral steroid use, hospital visits) | Arg16Arg genotypes were at greatest risk |
Turner [49] | Multiethnic | ICS, LABA, LTM combinations | Exacerbation (varies based on study) | Arg16 variants receiving ICS + LABA were at greater risk |
Alghobashy [26] | Egypt | ICS + LABA | FEV1 and FEV1/FVC | Gly16Gly and Glu27Glu produced unfavorable response |
Study | Population | Gene | Medication | Measurement | Results |
---|---|---|---|---|---|
Tantisira [51] | White | GLCCI1 | Budesonide | Change in FEV1 from baseline | rs37972 TT and rs37973 G allele variants showed unfavorable responses |
Thompson [52] | European | GLCCI1 | ICS | Exacerbation (hospital visits and oral steroid use) | rs37973 G allele showed unfavorable response |
Vijverberg [53] | Europe | GLCCI1 | Budesonide | Exacerbation (emergency room visits, hospital visits, oral steroid use) | No association found at rs37972 |
Huang [54] | Chinese | GLCCI1 | ICS | MMEF | rs37969, rs37972, and rs37973 produced favorable response. |
Kim [55] | Korean | HDAC1 | ICS | % change in FEV1 pre- and post-bronchodilator | rs1741981 CT and TT produced favorable response |
Tantisira [56] | Caucasians | CRHR1 | Budesonide | % change in FEV1 from baseline | rs242941T produced favorable response |
Tantisira [57] | Multiethnic | TBX21 | Budesonide | % change in FEV1 and PC20 | rs2240017Q produced favorable response |
Tantisira [58] | Multiethnic | FCER2 | Budesonide | Exacerbations (ER visits or hospitalization) | rs28364072 CC produced unfavorable response |
Koster [59] | European | FCER2 | ICS, ICS + salmeterol, ICS + salmeterol + montelukast | Exacerbations (hospital visits and/or oral steroid use) | rs28364072 CC produced unfavorable response |
Keskin [60] | Turkey | NR3C1 | Fluticasone | FEV1 improvement at 4 h | rs41423247 GG produced favorable response |
Stockman [61] | Whites | CYP3A4, CYP3A5, and CYP3A7 | Fluticasone | Asthma control scores | CYP3A4 *22 produced favorable response |
Stockman [62] | White | CYP3A4, CYP3A5, and CYP3A7 | Beclomethasone | Asthma control scores | CYP3A5 *3/*3 produced favorable response |
Study | Population | Gene | Measurement | Results |
---|---|---|---|---|
Kim [67] | Korean | TBXA2 | FEV1 | Combination of +795 CT/CC and +924 TT showed unfavorable response |
Klotsman [69] | Multiethnic | ALOX5 CystLTR2 LTC4S | PEF PEF FEV1 and PEF | rs4987105 TT and rs4986832 AA variants showed favorable outcomes rs912277 TT and rs912278 TC variants produced favorable response No association found at rs730012 |
Telleria [70] | Spain | ALOX5 | % change in FEV1, exacerbations, and rescue inhaler need | rs59439148 5/5 and 5/4 copies showed favorable outcomes |
Kang [71] | Korean | LTC4S PTGDR | ≥10% increase in FEV1 post exercise challenge | No significance at rs730012 rs803010 TT produced favorable response |
Lee [72] | Korean | LTC4S CystLTR1 | >10% increase in FEV1 post exercise challenge | No significance at SNP rs730012 No significance found |
Whelan [73] | African American and Caucasian | LTC4S | FENO | rs730012 AC produced favorable response |
Mougey [74] | Multiethnic | SLCO2B1 | Asthma symptom utility index (ASUI) | rs12422149 GG produced favorable response No association at rs2306168 |
Li [75] | Chinese | SLCO2B1CYP2C8 | Drug clearance | Decreased clearance in rs12422149 GG No association found |
Study | Population | Gene | Medication | Measurement | Results |
---|---|---|---|---|---|
Lipworth [47] | Scotland | ADRB2 | Fluticasone + montelukast or salmeterol + fluticasone | School absences, FEV1, asthma symptoms | Arg16Arg produced favorable responses to fluticasone and montelukast |
Study | Population | Gene | Medication | Measurement | Results |
---|---|---|---|---|---|
Tcheurekdjlan [79] | Mexican and Puerto Ricans | LTA4H ALOX5AP | Albuterol + leukotriene modifiers (montelukast, zafirlukast, and zileuton) | % change in FEV1 pre and post bronchodilator | LTA4H rs2540491 A variants and rs2540487 GA variants produced favorable response No association of ALOX5AP variants alone rs10507391 A allele and rs9551963 C allele magnifies LTA4H response |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Lim, C.; Priefer, R. Pharmacogenomics and Pediatric Asthmatic Medications. J. Respir. 2022, 2, 25-43. https://doi.org/10.3390/jor2010003
Lim C, Priefer R. Pharmacogenomics and Pediatric Asthmatic Medications. Journal of Respiration. 2022; 2(1):25-43. https://doi.org/10.3390/jor2010003
Chicago/Turabian StyleLim, Christy, and Ronny Priefer. 2022. "Pharmacogenomics and Pediatric Asthmatic Medications" Journal of Respiration 2, no. 1: 25-43. https://doi.org/10.3390/jor2010003