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03.09.2018 | ASTHMA

Beta 2 Adrenergic Receptor Genetic Polymorphisms in Bronchial Asthma: Relationship to Disease Risk, Severity, and Treatment Response

verfasst von: Aliaë A. R. Mohamed-Hussein, Suzan S. Sayed, Heba M. Saad Eldien, Azza M. Assar, Fatma E. Yehia

Erschienen in: Lung | Ausgabe 6/2018

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Abstract

Background

The β₂-adrenergic receptor gene is one of the most extensively studied genes with respect to asthma prevalence and severity. The Arg16Gly and Gln27Glu polymorphisms in the β₂-adrenergic receptor gene cause changes in the amino acids sequence of the receptor which may cause alteration in response to bronchodilators and the risk of asthma.

Objective

The purpose of the study was to determine the association between β₂-adrenergic receptor gene polymorphisms and asthma risk, severity and response to therapy.

Subjects and Methods

58 asthmatic patients and 38 healthy subjects were included. The β₂-adrenergic receptor polymorphisms genotyping was done using Real-Time polymerase chain reaction.

Results

The allelic frequencies for the Arg16Gly polymorphism were 15.5%, 48.3%, and 36.2% for the homozygous A wild, heterozygous, and homozygous G mutant alleles in asthmatics (P < 0.01) and 5.3%, 47.4%, and 47.4% in healthy subjects (P < 0.01). For the Gln27Glu polymorphism, the allelic frequencies for the homozygous C wild, heterozygous and homozygous G mutant alleles were 51.7%, 41.4%, and 6.9% in asthmatics (P < 0.01) and 44.7%, 39.5%, and 15.8% in healthy subjects (P < 0.01). The heterozygous Arg16Gly and Gln27Glu were found in most of severe asthma cases (7/13, 53.8% each). While homozygous wild and mutant seemed to be protective and associated with mild disease in both alleles. Finally, 75% of Arg16Gly heterozygous group were good responders (P < 0.01), 81% of homozygous G mutant were bad responders. For Gln27Glu polymorphism, 60% of C wild group were good responders and 75% of G mutant group were bad responders.

Conclusions

The findings suggest that the Arg16Gly and Gln27Glu polymorphisms in the β2-AR gene are associated with asthma severity and response to therapy and might be used in personalized treatment for these patients in the future. This work is registered in ClinicalTrial.gov with ID: NCT03118869.

Global Initiative for Asthma [homepage on the internet]. Global strategy for asthma management and prevention, © 2017. http://ginasthma.org/2017-gina-report-global-strategy-for-asthma-management-and-prevention/. Accessed 6 July 2017

De Paiva A, Marson F, Ribeiro J.et al (2014) Asthma: Gln27Glu and Arg16Gly polymorphisms of the beta2-adrenergic receptor gene as risk factors. Allergy Asthma Clin Immunol 10:8. https://doi.org/10.1186/1710-1492-10-8 CrossRefPubMedPubMedCentral

Liang S, Chen X, Deng J et al (2014) Beta-2 Adrenergic Receptor (Β2-AR) Gene polymorphisms and the risk of asthma: a meta-analysis of case-control studies. PLoS ONE 9:8. https://doi.org/10.1371/journal.pone.0104488 CrossRef

Adeloye D, Chan KY, Rudan I et al (2013) An estimate of asthma prevalence in Africa: a systematic analysis. Croat Med J Dec 54(6):519–531CrossRef

El-Mashad GM, Mahmoud AA, Abdel Hafez AA (2016) The prevalence of bronchial asthma among primary school children in Menoufiya Governorate (El-Bagour Center). Egypt J Med Hum Genet 29(1):89–94. https://doi.org/10.4103/1110-2098.178992 CrossRef

Abdallah A, Sanusy K, Said W et al (2012) Epidemiology of bronchial asthma among preparatory school children in Assiut district. Egypt J Pediatr Allergy Immunol 10(2):109–117

Barnes KC (2011) Genetic studies of the etiology of asthma. Proc Am Thorac Soc 8:143–148CrossRef

Liggett SB (2000) The pharmacogenetics of β2-adrenergic receptors: relevance to asthma. J Allergy Clin Immunol 105:487–492. https://doi.org/10.1016/S0091-6749(00)90048-4 CrossRef

Billington CK, Penn RB, Hall IP (2016) β2 Agonists. In: Page C, Barnes P (eds) Pharmacology and therapeutics of asthma and COPD. Handbook of experimental pharmacology, Springer, Cham

10.

Ortega VE, Meyers DA (2014) Implications of population structure and ancestry on asthma genetic studies. Curr Opin Allergy Clin Immunol 14(5):381–389. https://doi.org/10.1097/ACI.0000000000000102 CrossRefPubMedPubMedCentral

11.

Holloway JW, Dunbar PR, Riley GA et al (2000) Association ofβ2-adrenergic receptor polymorphisms with severe asthma. Clin Exp Allergy 30:1097–1103. https://doi.org/10.1046/j.1365-2222.2000.00929.x CrossRefPubMed

12.

Turki J, Pak J, Green SA et al (1995) Genetic polymorphisms of the beta 2-adrenergic receptor in nocturnal and non-nocturnal asthma. Evidence that Gly16 correlates with the nocturnal phenotype. J Clin Invest 95:1635–1641. https://doi.org/10.1172/JCI117838 CrossRefPubMedPubMedCentral

13.

Contopoulos-Ioannidis DG, Manoli EN, Ioannidis JPA (2005) Meta-analysis of the association ofb2-adrenergic receptor polymorphisms with asthma phenotypes. J Allergy Clin Immunol 115(5):963–972. https://doi.org/10.1016/j.jaci.2004.12.1119 CrossRefPubMed

14.

Salah K, Morsy S, Atta A (2012) Effects of β2-adrenergic receptor polymorphisms on asthma severity and response to salbutamol in Egyptian children. Egypt J Pediatr Allergy Immunol 10(2):81–86

15.

Palmer CNA, Lipworth BJ, Lee S et al (2006) Arginine-16β2-adrenoceptor genotype predisposes to exacerbations in young asthmatics taking regular salmeterol. Thorax 61:940–944. https://doi.org/10.1136/thx.2006.059386 CrossRefPubMedPubMedCentral

16.

Fu WP, Zhao ZH, Zhong L et al (2011) Relationship between polymorphisms in the 5′ leader cistron, positions 16 and 27 of the adrenergicß2 receptor gene and asthma in a Han population from southwest China. Respirology 16:1221–1227. https://doi.org/10.1111/j.1440-1843.2011.02028.x CrossRefPubMed

17.

National Center for Biotechnology Information. http://www.ncbi.nlm.nih.gov/

18.

Hizawa N (2009) Beta-2 adrenergic receptor genetic polymorphisms and asthma. J Clin Pharm Ther 34:631–643. https://doi.org/10.1111/j.1365-2710.2009.01066.x CrossRefPubMed

19.

Karam RA, Sabbah NA, Zidan HE et al (2013) Association between genetic polymorphisms of ß2 adrenergic receptors and nocturnal asthma in Egyptian children. J Investig Allergol Clin Immunol 23(4):262–266PubMed

20.

Birbian N, Singh J, Jindal S et al (2012) Association of ß2-adrenergic receptor polymorphisms with asthma in a north. Indian Popul Lung 190:497–504. https://doi.org/10.1007/s00408-012-9407-7 CrossRef

21.

Larocca N, Moreno D, Garmendia JV,et al (2013) 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 157(4):374–378. https://doi.org/10.5507/bp.2012.084 CrossRefPubMed

22.

Lee MY, Cheng SN, Chen SJ et al (2011) Polymorphisms of the b2-adrenergic receptor correlated to nocturnal asthma and the response of terbutaline nebulizer. Pediatr Neonatol 52:18–23. https://doi.org/10.1016/j.pedneo.2010.12.011 CrossRefPubMed

23.

Lin YC, Lu CC, Shen CY et al (2003) Roles of genotypes of b2-adrenergic receptor in the relationship between eosinophil counts and lung function in Taiwanese adolescents. J Asthma 40(3):265–272. https://doi.org/10.1081/JAS-120018323 CrossRefPubMed

24.

Salama MS, Ashaat NA, Hamad AA (2011) Genetic association between common beta-2adrenoreceptor polymorphism and asthma severity in school-age children. Egypt J Med Hum Genet 12:151–156. https://doi.org/10.1016/j.ejmhg.2011.07.003 CrossRef

25.

Reihsaus E, Innis M, MacIntyre N et al (1993) Mutations in the gene encoding for the β2-adrenergic receptor in normal and asthmatic subjects. Am J Respir Cell Mol Biol 8:334–339. https://doi.org/10.1165/ajrcmb/8.3.334 CrossRefPubMed

26.

Dewar JC, Wheatley AP, Venn A et al (1998) β2-adrenoceptor polymorphisms are in linkage disequilibrium, but are not associated with asthma in an adult population. Clin Exp Allergy 28:442–448. https://doi.org/10.1046/j.1365-2222.1998.00245.x CrossRefPubMed

27.

Hakonarson H, Bjornsdottir US, Ostermann E et al (2001) Allelic frequencies and patterns of single-nucleotide polymorphisms in candidate genes for asthma and atopy in Iceland. Am J Respir Crit Care Med 164:2036–2044CrossRef

28.

Schachor J, Ziv C, Varsano S et al (2003) Genetic polymorphisms of the beta 2 adrenergic receptor in Israelis with severe asthma compared to non-Asthmatic Israelis. Isr Med Assoc J 5(11):821–824

29.

Hall IP, Wheatley A, Wilding P et al (1995) Association of Glu 27β2-adrenoceptor polymorphism with lower airway reactivity in asthmatic subjects. Lancet 345:1213–1214. https://doi.org/10.1016/S0140-6736(95)91994-5 CrossRefPubMed

30.

Green SA, Turki J, Innis M et al (1994) Amino-terminal polymorphisms of the human β2-adrenergic receptor impart distinct agonist-promoted regulatory properties. Biochemistry 33:9414–9419. https://doi.org/10.1021/bi00198a006 CrossRefPubMed

31.

Lima JJ, Thomason DB, Mohamed MHN et al (1999) Impact of genetic polymorphisms of theβ2-adrenergic receptor on albuterol bronchodilator pharmacodynamics. Clin Pharmacol Ther 65(5):519–525. https://doi.org/10.1016/S0009-9236(99)70071-8 CrossRefPubMed

32.

Summerhill E, Leavitt SA, Gidley H et al (2000) β2-Adrenergic receptor Arg16/Arg16 genotype is associated with reduced lung function, but not with asthma, in the hutterites. Am J Respir Crit Care Med 162:599–602. https://doi.org/10.1164/ajrccm.162.2.9910108 CrossRefPubMed

33.

Telleria JJ, Blanco-Quiros A, Muntion S et al (2006) Tachyphylaxis to β2-agonists in Spanish asthmatic patients could be modulated by β2-adrenoceptorgene polymorphisms. Respir Med 100:1072–1078. https://doi.org/10.1016/j.rmed.2005.09.028 CrossRefPubMed

34.

Qiu Y, Zhang D, Qin Y et al (2014) Effect of β2 -adrenergic receptor gene Arg16Glypolymorphisms on response to long-acting β2-agonist in Chinese Han asthmatic patients. Multidiscip Respir Med 9:22–25CrossRef

35.

Chong LK, Chowdry J, Ghahramani P et al (2000) Influence of genetic polymorphisms in the β2-adrenoceptor on desensitization in human lung mast cells. Pharmacogenetics 10(2):153–162CrossRef

36.

Kay LJ, Rostami-Hodjegan A, Suvarna SK et al (2007) Influence of β2-adrenoceptor gene polymorphisms on β2-adrenoceptor-mediated responses in human lung mast cells. Br J Pharmacol 152:323–331. https://doi.org/10.1038/sj.bjp.0707400 CrossRefPubMedPubMedCentral

Titel: Beta 2 Adrenergic Receptor Genetic Polymorphisms in Bronchial Asthma: Relationship to Disease Risk, Severity, and Treatment Response
verfasst von: Aliaë A. R. Mohamed-Hussein
Suzan S. Sayed
Heba M. Saad Eldien
Azza M. Assar
Fatma E. Yehia
Publikationsdatum: 03.09.2018
Verlag: Springer US
Erschienen in: Lung / Ausgabe 6/2018
Print ISSN: 0341-2040
Elektronische ISSN: 1432-1750
DOI: https://doi.org/10.1007/s00408-018-0153-3

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Beta 2 Adrenergic Receptor Genetic Polymorphisms in Bronchial Asthma: Relationship to Disease Risk, Severity, and Treatment Response

Abstract

Background

Objective

Subjects and Methods

Results

Conclusions

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Abstract

Background

Objective

Subjects and Methods

Results

Conclusions

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