The state of studying the polymorphism of individual genes in the development of bronchial asthma
DOI:
https://doi.org/10.15574/SP.2024.138.74Keywords:
children, bronchial asthma, polymorphism, gene, β2-adrenoceptorsAbstract
The study of the polymorphism of individual genes is the basis of both preventive medicine and is used in the selection of adequate therapy. Polymorphism of individual candidate genes in bronchial asthma (BA) is studied taking into account many personal characteristics and the influence of environmental factors.
Aim - to analyze the status of the study of the role of polymorphism of β2-adrenoceptors (ADRβ2) in the pathogenesis of bronchial asthma in children and to compare them with our own findings.
Materials and methods. The results of research on polymorphism of individual genes in children with BA, which includes the PubMed database, were analyzed. An in-depth study of the anamnesis data (disease, life, hereditary), a complex clinical and laboratory examination of children (n=101) of school age with BA was carried out (the average age was: for boys 11.15±0.48 years; for girls - 10.63±0.7 years). Patients were diagnosed with BA in accordance with the GINA recommendations of the current revision. Determination of the Arg16Gly polymorphism of the ADRβ2 gene (rs 1042713) was performed by the polymerase chain reaction method followed by restriction enzyme analysis. The obtained data were processed in the Statsoft STATISTICA software package. Mean values were given as (M±m), Student's test was used for comparison.
Results. The assessment of the frequency of polymorphism of the Arg16Gly gene in BA established that two variants prevailed in boys: Arg16Gly and Gly16Gly; at that time, the Gly16Gly genotype prevailed among girls, which, according to individual studies, is associated with good effectiveness of the applied therapy (nebulization of salbutamol). Mutations in the ADRβ2 gene in patients with BA were twice as frequent in the Arg16Gly genotype and three times as frequent in the Gln27Glu genotype, in contrast to healthy children. Such a polymorphism affects the functional activity of ADRβ2, the occurrence and course of BA.
Conclusions. The Arg16Gly polymorphism of the ADRβ2 gene in children with BA largely determines the sensitivity of ADRβ2 to the applied exacerbation therapy and the effectiveness of basic treatment. In patients with the Gly16Gly genotype, most researchers note the good clinical effectiveness of both fast broncholytic drugs (β2 short-acting agonists) and basic anti-inflammatory drugs. The diagnosed homozygous Arg16Arg genotype of the ADRβ2 gene mostly accompanies the uncontrolled (or partially controlled) course of asthma in children. The revealed features of the Arg16Gly polymorphism of the ADRβ2 gene will help the doctor to draw up an adequate treatment plan, which is based on the genetically determined sensitivity of ADRβ2 receptors to medical preparations.
The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies.
No conflict of interests was declared by the author.
References
Banadyha NV. (2018). Genotypic course features of the various bronchial asthma phenotypes in children. Sovremennaya pediatriya. 6(94): 9-13. https://doi.org/10.15574/SP.2018.94.9
Banadyha NV, Voloshyn SB. (2016). Bronchial asthma emergency treatment in children including clinical aspects and gene polymorphism β2 adrenergic receptors. Sovremennaya pediatriya. 8(80): 65-69. https://doi.org/10.15574/SP.2016.80.65
Banadyha NV. (2020). The role of individual gene polymorphism in the formation of bronchial asthma in children. Current Issues of Pediatrics, Obstetrics and Gynecology. 1: 5-9. https://doi.org/10.11603/24116-4944.2020.1.11476
Carroll CL, Stoltz P, Schramm CM et al. (2009). Beta2adrenergic receptor polymorphisms affect response to treatment in children with severe asthma exacerbations. Chest. 135: 1186-1192. https://doi.org/10.1378/chest.08-2041; PMid:19029431
Del Giudice MM, Allegorico A, Grandone A et al. (2015, Apr-Jun). Vitamin D and bronchial inflammation in asthmatic children. J Biol Regul Homeost Agents. 29; 2 Suppl 1: 125-129.
Despotovic M, Jevtovic Stoimenov T, Stankovic I et al. (2017). Vitamin D Receptor Gene Polymorphisms in Serbian Patients With Bronchial Asthma: A Case-Control Study. J Cell Biochem. 118: 3986-3992. https://doi.org/10.1002/jcb.26054; PMid:28407346
Everman JL, Sajuthi S, Saef B et al. (2019). Functional genomics of CDHR3 confirms its role in HRV-C infection and childhood asthma exacerbations. J Allergy Clin Immunol. 144: 962-971. https://doi.org/10.1016/j.jaci.2019.01.052; PMid:30930175 PMCid:PMC6766426
Han JC, Du J, Zhang YJ, Qi GB, Li HB et al. (2016, Oct). Vitamin D receptor polymorphisms may contribute to asthma risk. J Asthma. 53(8): 790-800. https://doi.org/10.3109/02770903.2016.1158267; PMid:27088875
Holster A, Teräsjärvi J, Lauhkonen E et al. (2018). IL-17A gene polymorphism rs2275913 is associated with the development of asthma after bronchiolitis in infancy. Allergol Int. 67: 109-113. https://doi.org/10.1016/j.alit.2017.05.010; PMid:28647382
Kanazawa J, Masuko H, Yatagai Y et al. (2017). Genetic association of the functional CDHR3 genotype with early-onset adult asthma in Japanese populations. Allergol Int. 66: 563-567. https://doi.org/10.1016/j.alit.2017.02.012; PMid:28318885
Karimi LL, Vijverberg SJ, Engelkes M et al. (2021). ADRB2 haplotypes and asthma exacerbations in children and young adults: An individual participant data meta-analysis. Clinical & Experimental Allergy. 51(3). https://doi.org/10.1111/cea.13965; PMid:34128573 PMCid:PMC8503671
Liang SQ, Chen XL, Deng JM et al. (2014). Beta-2 adrenergic receptor (ADRB2) gene polymorphisms and the risk of asthma: a meta-analysis of case-control studies. PLoS One. 9: e104488. https://doi.org/10.1371/journal.pone.0104488; PMid:25111792 PMCid:PMC4128804
Lim Ch, Priefer R. (2022). Pharmacogenomics and Pediatric Asthmatic Medications. J. Respir. 2(1): 25-43. https://doi.org/10.3390/jor2010003
Mohammed AS, Abood HAN, Abood HAN. (2021). The Effect of 16 Arg/Gly β2-Adrenergic Receptors Gene Polymorphism on Pulmonary Function in Asthmatic Children Treated with Nebulized Salbutamol. June .Biomedical and Biotechnology Research Journal (BBRJ). 5(2): 161-165. https://doi.org/10.4103/bbrj.bbrj_36_21
Moore PE, Laporte JD, Abraham JH et al. (2000). Polymorphism of the beta(2)-adrenergic receptor gene and desensitization in human airway smooth muscle. Am J Respir Crit Care Med. 162: 2117-2124. https://doi.org/10.1164/ajrccm.162.6.9909046; PMid:11112125
Muchão FP, Souza AV, Souza JME et al. (2022, Mar 25). Association between beta-2 adrenergic receptor variants and clinical outcomes in children and adolescents with acute asthma. Einstein (Sao Paulo). 20: eao6412. https://doi.org/10.31744/einstein_journal/2022AO6412; PMid:35352766 PMCid:PMC8932728
Nieto-Fontarigo JJ, Salgado FJ, San-José ME et al. (2018). The CD14 (-159 C/T) SNP is associated with scd14 levels and allergic asthma, but not with CD14 expression on monocytes. Sci Rep. 8: 4147. https://doi.org/10.1038/s41598-018-20483-1; PMid:29515128 PMCid:PMC5841440
Perez-Garcia OJ, Espuela-Ortiz A, Lorenzo-Diaz F, Pino-Yanes M. (2020). Pharmacogenetics of Pediatric Asthma: Current Perspectives.Pharmgenom. Pers. Med. 13: 89-103. https://doi.org/10.2147/PGPM.S201276; PMid:32256100 PMCid:PMC7090194
Shi F, Zhang Y, Qiu C. (2022). Gene polymorphisms in asthma: a narrative review. Ann Transl Med. 10(12): 711. https://doi.org/10.21037/atm-22-2170; PMid:35845533 PMCid:PMC9279821
Slob EMA, Richards LB, Vijverberg SJH et al. (2021). Genome‐wide association studies of exacerbations in children using long‐acting beta2‐agonists. Pediatric Allergy and Immunology. 32(11). https://doi.org/10.1111/pai.13494; PMid:33706416 PMCid:PMC8328929
Vince N, Limou S, Daya M et al. (2020). Association of HLA-DRB1*09:01 with tige levels among African-ancestry individuals with asthma. J Allergy Clin Immunol. 146: 147-155. https://doi.org/10.1016/j.jaci.2020.01.011; PMid:31981624
Wang D, Yang Y, Xu J et al. (2016). Association of CD14 -159 (-260C/T) polymorphism and asthma risk: an updated genetic meta-analysis study. Medicine (Baltimore). 95: e4959. https://doi.org/10.1097/MD.0000000000004959; PMid:27684840 PMCid:PMC5265933
Wechsler ME, Kunselman SJ, Chinchilli VM et al. (2009). Effect of beta2-adrenergic receptor polymorphism on response to longacting beta2 agonist in asthma (LARGE trial): a genotype-stratified, randomised, placebo-controlled, crossover trial. Lancet. 374: 1754-1764.
Yao Y, Zhu L, Li J et al. (2016). Association of HLA-DRB1 Gene Polymorphism with Risk of Asthma: A Meta-Analysis. Med Sci Monit Basic Res. 22: 80-86. https://doi.org/10.12659/MSMBR.900193; PMid:27503745 PMCid:PMC4989996
Zhao S, Zhang W, Nie X. (2019). Association of β2-adrenergic receptor gene polymorphisms (rs1042713, rs1042714, rs1042711) with asthma risk: a systematic review and updated meta-analysis. BMC Pulm Med. 19: 202. https://doi.org/10.1186/s12890-019-0962-z; PMid:31699066 PMCid:PMC6836544
Zhu M, Wang T, Chen R et al. (2016). Association between interleukin-17a gene polymorphisms and asthma risk: a meta-analysis. Asian Pac J Allergy Immunol. 34: 115-123. https://doi.org/10.12932/AP0680.34.2.2016
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