Abstract
Background
Alterations of B2 adrenergic receptor (β2AR) can modulate the severity of asthma and the response to treatment. Therefore, we aimed to evaluate β2AR gene polymorphism at codons 16 and 27 and their effect on asthma severity and response to treatment in asthmatic children.
Methods
Case–control study was conducted on 156 children; 104 of them had bronchial asthma and 52 were healthy children (control group). Subjects of the study underwent history taking, clinical examination, pulmonary function tests, serum IgE level assessment, and identification of β2AR-16 A46G and β2AR-27 C79G polymorphism using PCR-Restriction Fragment length polymorphisms (RFLP) test.
Results
There was a higher frequency of Arg–Gly genotypes (odds ratio (OR)=6.57; confidence interval (CI): 2.42–18.81, P<0.001) and lower frequency of Arg–Arg (OR=4.7; CI: 2.05–10.95, P<0.001) among asthmatic children compared with that among controls at codon 16. The presence or absence of Gly16 or Glu27 either homozygous or heterozygous for both correlated with the grade of asthma severity. The presence of heterozygous Arg–Gly and Gln–Glu gives a better response to drug therapy than the presence of Gly–Gly and Glu–Glu genotypes at codons 16 and 27.
Conclusion
Polymorphism of β2AR at codons 16 and 27 correlates with asthma severity and response to treatment in asthmatic children.
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References
Global Initiative for Asthma. Global strategy for asthma management and prevention. National Institute of Health (NIH) Publication, 2008. (HTTP://inasthma.org).
Isaza C, Sepulveda Arias JC, Agudelo BL et al. B2 adrenoreceptor polymorphism in asthmatic and non-asthmatic school children from Colombia and their relationship to treatment response. Pediatr Pulmonol 2012;47:848–55.
Van Veen A, Wierenga EA, Westland R et al. Limited beta-2-adrenoceptor haplotypes display different agonist-mediated airway responses in asthmatics. Respir Res 2006;7:19.
Hawkins GA, Weiss ST, Bleecker ER et al. Clinical consequences of ADRb2 polymorphisms. Pharmacogenomics 2008;9:349–58.
Carroll CL, Stoltz P, Schramm CM et al. Beta-2-adrenergic receptor polymorphisms affect response to treatment in children with severe asthma exacerbations. Chest 2009;135:1186–92.
Moore PE, Laporte JD, Abraham JH et al. Polymorphisms of the b2-adrenergic receptor gene and desensitization in human airway smooth muscle. Am J Respir Crit Care Med 2000;162:2117–24.
Asano K, Yamada-Yamasawa W, Kudoh H et al. Association between beta-adrenoceptor gene polymorphisms and relative response to beta(2)-agonists and anticholinergic drugs in Japanese asthmatic patients. Respirology 2010;15:849–54.
Zhang G, Hayden CM, Khoo SK et al. B2-adrenoceptor polymorphisms and asthma phenotypes; Interactions with passive smoking. Eur Respir J 2007;30:48–55.
Wechsler ME, Kunselman SJ, Chinchilli VM et al. Effect of beta-2-adrenergic receptor polymorphism on response to long-acting beta-2 agonist in asthma (LARGE trial): a genotype-stratified, randomized, placebo-controlled, crossover trial. Lancet 2009;374:1754–64.
Martin AC, Zhang G, Rueter K et al. Beta-2-adrenoceptor polymorphisms predict response to beta-2-agonists in children with acute asthma. J Asthma 2008;45:383–8.
Global initiative for asthma: global strategy for asthma management and prevention, 2006. (HTTP://inasthma.org).
Plebani M, Bernardi D, Basso D et al. Measurement of immunoglobulin E: intermethod comparison and standardization. Clin Chem 1998;44:1974–9.
Miller SA, Dykes DD, Polesky HF et al. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988;16:1215.
Ahn SJ, Costa J, Emanuel JR . PicoGreen quantitation of DNA: effective evaluation of samples pre- or post-PCR. Nucleic Acids Res 1996;24:2623–5.
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;100:3184–8.
Silvers SK, Lang DM . Asthma in African Americans: what can we do about the higher rates of disease? J Med 2012;79:193–201.
Hizawa N . Pharmacogenetic of B2-agonist. Allergol Int 2011;60:239–46.
Salama MS, Ashaat NA, Hamad AA . Genetic association between common beta-2 adrenoreceptor polymorphism and asthma severity in school-age children. Egypt J Med Hum Genet 2011;12:1–6.
Al-Rubaish A . B2 adrenergic receptor gene polymorphism in the normal and asthmatic individual in the Eastern individual province Saudi Arabia. Ann Saudi Med 2011;31:586–90.
Salah K, Morsy S, Atta A . Effects of ADRB2 polymorphism on asthma severity and response to salbutamol on Egyptian children. Egypt J Pediatr Allergy Immunol 2012;10:81–6.
Larocca N, Moreno D, Garmendia JV et al. Beta 2 adrenergic receptor polymorphisms, at codons 16 and 27, and bronchodilator responses in adult Venezuelan asthmatic patients. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2012;156:374–8.
Manoli EN, Contopoulos-Ioannidis DG, Ioannidis JP . Meta-analysis of the association of beta2-adrenergic receptor polymorphisms with asthma phenotypes. J Allergy Clin Immunol 2005;115:963–72.
de Paiva AC, Marson FA, Ribeiro JD, Bertuzzo CS . Asthma Gln27Glu and Arg16Gly polymorphisms of the beta2-adrenergic receptor gene as risk factors. Allergy Asthma Clin Immunol 2014;10:8.
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;268:23116–21.
Karam RA, Sabbah NA, Zidan HE, Rahman HMA . Association between genetic polymorphisms of ß2 adrenergic receptors and nocturnal asthma in Egyptian children. J Investig Allergol Clin Immunol 2013;23:262–6.
Giubergia V, Zelazko M, Roy A et al. β2-adrenergic polymorphisms and total serum IgE levels in children with asthma from Argentina. Ann Allergy Asthma Immunol 2009;102:308–13.
Wang C, Salam MT, Islam T et al. Effects of in utero and childhood tobacco smoke exposure and beta2-adrenergic receptor genotype on childhood asthma and wheezing. Pediatrics 2008;122:107–14.
Litonjua AA, Silverman EK, Tantisira KG et al. β2-Adrenergic receptor polymorphisms and haplotypes are associated with airways hyper responsiveness among nonsmoking men. Chest 2004;126:66–74.
Park HW, Yang MS, Park CK et al. The additive role of ipratropium in severe asthmatics and Arg16Gly in ADRB2 as a potential marker to predict response. Allergy 2009;64:778–83.
Finkelstein Y, Garcia Bournissen F, Hutson J et al. Polymorphism of B2ADR gene and response to inhaled beta-agonists in children with asthma: a meta-analysis. Asthma 2009;46:900–5.
Castro-Giner F, Gonzalez JR, Jarvis D et al. Position ally cloned genes and age specific effects in asthma and atopy: an international population-based cohort study (ECRHS). Thorax 2009;65:124–31.
Kim SH, Lee HY, Sh Lee et al. Effect of B2 adrenergic receptor polymorphism in asthma control of patient receiving combination treatment. Yonsei Med J 2009;50:182–8.
Bleecker ER, Postma DS, Lawrence RM et al. Effect of ADRB2 polymorphisms on response to long-acting β2-agonist therapy. Lancet 2007;370:2118–25.
Silverman EK, Kwiatkowski DJ, Sylvia JS et al. Family-based association analysis of β2-adrenergic receptor polymorphisms in the childhood asthma management program. J Allergy Clin Immunol 2003;112:870–6.
Snyder EM, Beck KC, Dietz NM et al. Influence of B2-adrenergic receptor genotype on airway function during exercise in a healthy adult. Chest 2006;129:762–70.
Abramson MJ, Walters J, Walters EH . Adverse effects of β-agonists: are they clinically relevant. Am J Respir Med 2003;2:287–97.
Lipworth B . Benefit-risk assessment of long-acting β2-agonists in asthma. Drug Saf 2004;27:243–70.
Bleecker ER, Nelson HS, Kraft M et al. Beta 2-receptor polymorphism in patients receiving salmeterol with or without fluticasone propionate. Am J Respir Crit Care Med 2010;181:676–87.
Wechsler ME, Lehman E, Lazarus SC et al. β2-adrenergic receptor polymorphisms and response to salmeterol. Am J Respir Crit Care Med 2006;173:519–26.
Rebordosa C, Kogevinas M, Guerra S et al. ADRB2 Gly16Arg polymorphism, asthma control, and lung function decline. Eur Respir J 2011;38:1029–35.
Qiu Y, Zhang D, Qin Y et al. Effect of β2 -adrenergic receptor gene Arg16Gly polymorphisms on response to long-acting β2-agonist in Chinese Han asthmatic patients. Multidiscip Respir Med 2014;9:22.
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Alghobashy, A., Elsharawy, S., Alkholy, U. et al. B2 adrenergic receptor gene polymorphism effect on childhood asthma severity and response to treatment. Pediatr Res 83, 597–605 (2018). https://doi.org/10.1038/pr.2017.304
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DOI: https://doi.org/10.1038/pr.2017.304