Gene Polymorphisms and Salbutamol Responsiveness in Serbian Children with Asthma

Overview

Journal Balkan J Med Genet

Publisher Sciendo

Specialty Genetics

Date 2018 Nov 15

PMID 30425908

Citations 1

Authors

N Jovicic

T Babic

S Dragicevic

B Nestorovic

A Nikolic

Affiliations

Soon will be listed here.

Abstract

Inhaled β2 adrenergic receptor (β2-AR) agonists are the mainstay of asthma therapy. The β2-AR protein is encoded by the gene and variants within this gene can have significant consequences for modulating the response to asthma therapy. This cross-sectional study performed at the University Children's Hospital in Belgrade, included 54 children with asthma. The subjects were genotyped for ADRB2 +46A>G (Arg16Gly, rs1042713) and +79C>G (Gln27Glu, rs 1042714) polymorphisms and the association with asthma severity and response to inhaled salbutamol was examined. In Serbian asthmatic children, allele +46A was detected with a frequency of 41.7% and allele +79G was detected with a frequency of 23.1%. Allele +46G was found to be associated with a better response to inhaled salbutamol ( <0.05) and with mild form of asthma ( <0.05). Polymorphism ADRB2 +46A>G may be a determinant of asthma severity and response to salbutamol in children with asthma. We did not find any association of +79C>G polymorphisms with the asthma severity and bronchodilator response to inhaled salbutamol. The results of this study can be potentially useful for personalization of asthma treatment.

Citing Articles

Pharmacogenetics of Pediatric Asthma: Current Perspectives.

Perez-Garcia J, Espuela-Ortiz A, Lorenzo-Diaz F, Pino-Yanes M Pharmgenomics Pers Med. 2020; 13:89-103.

PMID: 32256100 PMC: 7090194. DOI: 10.2147/PGPM.S201276.

References

Carroll C, Stoltz P, Schramm C, Zucker A . Beta2-adrenergic receptor polymorphisms affect response to treatment in children with severe asthma exacerbations. Chest. 2008; 135(5):1186-1192. DOI: 10.1378/chest.08-2041. View

Turner S, Francis B, Vijverberg S, Pino-Yanes M, Maitland-van der Zee A, Basu K . Childhood asthma exacerbations and the Arg16 β2-receptor polymorphism: A meta-analysis stratified by treatment. J Allergy Clin Immunol. 2016; 138(1):107-113.e5. PMC: 4931969. DOI: 10.1016/j.jaci.2015.10.045. View

Martinez F, Graves P, 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. 1998; 100(12):3184-8. PMC: 508532. DOI: 10.1172/JCI119874. View

Birbian N, Singh J, Jindal S, Singla N . Association of β(2)-adrenergic receptor polymorphisms with asthma in a North Indian population. Lung. 2012; 190(5):497-504. DOI: 10.1007/s00408-012-9407-7. View

Baren J, Zorc J . Contemporary approach to the emergency department management of pediatric asthma. Emerg Med Clin North Am. 2002; 20(1):115-38. DOI: 10.1016/s0733-8627(03)00054-3. View

Fu W, Zhao Z, Zhong L, Sun C, Fang L, Liu L . Relationship between polymorphisms in the 5' leader cistron, positions 16 and 27 of the adrenergic β2 receptor gene and asthma in a Han population from southwest China. Respirology. 2011; 16(8):1221-7. DOI: 10.1111/j.1440-1843.2011.02028.x. View

Martin A, Zhang G, Rueter K, Khoo S, Bizzintino J, Hayden C . Beta2-adrenoceptor polymorphisms predict response to beta2-agonists in children with acute asthma. J Asthma. 2008; 45(5):383-8. DOI: 10.1080/02770900801971792. View

Green S, Turki J, Bejarano P, Hall I, Liggett S . 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. View

Choudhry S, Ung N, Avila P, Ziv E, Nazario S, Casal J . Pharmacogenetic differences in response to albuterol between Puerto Ricans and Mexicans with asthma. Am J Respir Crit Care Med. 2004; 171(6):563-70. DOI: 10.1164/rccm.200409-1286OC. View

10.

Contopoulos-Ioannidis D, Manoli E, Ioannidis J . Meta-analysis of the association of beta2-adrenergic receptor polymorphisms with asthma phenotypes. J Allergy Clin Immunol. 2005; 115(5):963-72. DOI: 10.1016/j.jaci.2004.12.1119. View

11.

Isaza C, Sepulveda-Arias J, Agudelo B, Arciniegas W, Henao J, Porras G . β(2) -adrenoreceptor polymorphisms in asthmatic and non-asthmatic schoolchildren from Colombia and their relationship to treatment response. Pediatr Pulmonol. 2012; 47(9):848-55. DOI: 10.1002/ppul.22521. View

12.

de Paiva A, Marson F, Ribeiro J, Bertuzzo C . Asthma: Gln27Glu and Arg16Gly polymorphisms of the beta2-adrenergic receptor gene as risk factors. Allergy Asthma Clin Immunol. 2014; 10(1):8. PMC: 3930554. DOI: 10.1186/1710-1492-10-8. View

13.

Marson F, Bertuzzo C, Ribeiro A, Ribeiro J . Polymorphisms in ADRB2 gene can modulate the response to bronchodilators and the severity of cystic fibrosis. BMC Pulm Med. 2012; 12:50. PMC: 3558405. DOI: 10.1186/1471-2466-12-50. View

14.

Petrovic-Stanojevic N, Topic A, Nikolic A, Stankovic M, Dopudja-Pantic V, Milenkovic B . Polymorphisms of beta2-adrenergic receptor gene in serbian asthmatic adults: effects on response to Beta-agonists. Mol Diagn Ther. 2014; 18(6):639-46. DOI: 10.1007/s40291-014-0116-1. View

15.

. Standardization of Spirometry, 1994 Update. American Thoracic Society. Am J Respir Crit Care Med. 1995; 152(3):1107-36. DOI: 10.1164/ajrccm.152.3.7663792. View

16.

Barnes K . Genetic studies of the etiology of asthma. Proc Am Thorac Soc. 2011; 8(2):143-8. PMC: 3131830. DOI: 10.1513/pats.201103-030MS. View

17.

Finkelstein Y, Bournissen F, Hutson J, Shannon M . Polymorphism of the ADRB2 gene and response to inhaled beta- agonists in children with asthma: a meta-analysis. J Asthma. 2009; 46(9):900-5. DOI: 10.3109/02770900903199961. View

18.

Szczepankiewicz A, Breborowicz A, Sobkowiak P, Kramer L, Popiel A . Role of ADRB2 gene polymorphism in asthma and response to beta(2)-agonists in Polish children. J Appl Genet. 2009; 50(3):275-81. DOI: 10.1007/BF03195683. View

19.

Moore P, Laporte J, Abraham J, Schwartzman I, Yandava C, Silverman E . Polymorphism of the beta(2)-adrenergic receptor gene and desensitization in human airway smooth muscle. Am J Respir Crit Care Med. 2000; 162(6):2117-24. DOI: 10.1164/ajrccm.162.6.9909046. View

20.

Chung L, Waterer G, Thompson P . Pharmacogenetics of β2 adrenergic receptor gene polymorphisms, long-acting β-agonists and asthma. Clin Exp Allergy. 2011; 41(3):312-26. DOI: 10.1111/j.1365-2222.2011.03696.x. View