ADRB2 gene polymorphism in children with asthma and obesity
https://doi.org/10.36604/1998-5029-2020-77-87-98
Abstract
Introduction. The peculiarity of the clinical course of asthma in obese children allowed to identify a special phenotype, when the presence and severity of obesity determine a more severe course of asthma, which can serve as a criterion for predicting the worst response to asthma therapy. Asthma, like obesity, is recognized as a classic example of multi-factorial diseases, which are based on a fairly complex gene network. Investigating the genetic basis of both of these complex traits and linking them to the asthma phenotype should improve our understanding of the overall genetic basis of these pathological disorders. Aim. Review of the literature containing research data on available candidate genes that match asthma and obesity to present the current state of the issue, understand the direction of research, and solve problems. Materials and methods. The analysis of publications containing the results of the study of the effect of ADRB2 gene polymorphisms on the course of asthma in obese patients was carried out. Results. The analysis data shows that in general, the literature data on this problem is contradictory. It is emphasized that the strength of the relationship between the presence of predisposition gene polymorphisms is not always sufficient to explain the relationship between asthma and obesity, which leaves many unresolved issues that require further study. Conclusion. The analysis of genetic markers of asthma and obesity indicates the need for a comprehensive approach to research, which will contribute to the improvement and optimization of diagnostic and therapeutic measures.
About the Authors
R. S. Telepneva
Khabarovsk Branch of Far Eastern Scientific Center of Physiology and Pathology of Respiration – Research Institute of Maternity and Childhood Protection
Russian Federation
Regina S. Telepneva, Postgraduate student
Russian Federation
Regina S. Telepneva, Postgraduate student
G. P. Evseeva
Khabarovsk Branch of Far Eastern Scientific Center of Physiology and Pathology of Respiration – Research Institute of Maternity and Childhood Protection
Russian Federation
Galina P. Evseeva, MD, PhD, D.Sc. (Med.), Deputy Director on Scientific Work, Main Staff Scientist of the Group of Health and Environmental Problems of Mother and Child Health
Russian Federation
Galina P. Evseeva, MD, PhD, D.Sc. (Med.), Deputy Director on Scientific Work, Main Staff Scientist of the Group of Health and Environmental Problems of Mother and Child Health
E. B. Nagovitsina
Khabarovsk Branch of Far Eastern Scientific Center of Physiology and Pathology of Respiration – Research Institute of Maternity and Childhood Protection
Russian Federation
Elena B. Nagovitsina, MD, PhD (Med.), Leading Staff Scientist of Molecular Genetic Diagnostics Group
Russian Federation
Elena B. Nagovitsina, MD, PhD (Med.), Leading Staff Scientist of Molecular Genetic Diagnostics Group
S. V. Suprun
Khabarovsk Branch of Far Eastern Scientific Center of Physiology and Pathology of Respiration – Research Institute of Maternity and Childhood Protection
Russian Federation
Stefaniya V. Suprun, MD, PhD, D.Sc. (Med.), Main Staff Scientist of the Group of Health and Environmental Problems of Mother and Child Health
Russian Federation
Stefaniya V. Suprun, MD, PhD, D.Sc. (Med.), Main Staff Scientist of the Group of Health and Environmental Problems of Mother and Child Health
O. A. Lebed’ko
Khabarovsk Branch of Far Eastern Scientific Center of Physiology and Pathology of Respiration – Research Institute of Maternity and Childhood Protection
Russian Federation
Olga A. Lebed’ko, MD, PhD, D.Sc. (Med.), Director
Russian Federation
Olga A. Lebed’ko, MD, PhD, D.Sc. (Med.), Director
References
1. Portelly M., Sayers I. Genetic basis for personalized medicine in asthma. Expert Rev. Respir. Med. 2012; 6(2):223–236. https://doi.org/10.1586/ers.12.9
2. Fiorino E.K., Brooks L.J. Obesity and respiratory diseases in childhood. Clin. Chest Med. 2009; 30(3):601–608. https://doi:10.1016/j.ccm.2009.05.010
3. Novikova V.P., Eglit A.E. Bronchial asthma and obesity in children. Voprosy detskoy dietologii = Pediatric Nutrition 2014; 12(3):46–51 (in Russian).
4. Potapova N.L., Gaymolenko I.N., Smolyakov Yu.N. Analysis of significant risk factors in children with severe bronchial asthma. Vopr. prakt. pediatr. = Clinical Practice in Pediatrics 2020; 15(1):35–41 (in Russian). https://doi:10.20953/1817-7646-2020-1-35-41
5. Vakhlamov V.A., Tyurikova A.V. Rationale for the Use of New Methods of Investigation of Metabolic Syndrome in the Diagnosis and Treatment of Patients with Broncho-Obstructive Diseases. Sovremennye tehnologii v medicine=Modern Technologies in Medicine 2015; 7(4):127–134 (in Russian). http://doi.org/10.17691/stm2015.7.4.17
6. Pribylov S.A. Samosudova L.V., Pribylova N.N., Makhova O.Y. Phenotypical heterogeneity of severe bronchial asthma and the analysis of its treatment in Kursk region. Kursk Scientific and Practical Bulletin "Man and His Health" 2016; (3):33–38 (in Russian). https://doi.org/10.21626/vestnik/2016-3/06
7. Pshennova V.S., Yejova I.S., Khir Beck M., Aleksandrov O.V. The respiratory system condition under obesity. Medical Journal of the Russian Federation = Russian Medical Journal 2012; (4):6–11 (in Russian).
8. Grasemann H. Metabolic origins of childhood asthma. Mol. Cell. Pediatr. 2015; 2(1):6. https://doi:10.1186/s40348-015-0017-3
9. Mineev V.N., Lalaeva T.M., Vasilyeva T.S., Trofimov V.I. Phenotype of bronchial asthma with obesity. Pulmonologiya 2012; (2):102–107 (in Russian). https://doi.org/10.18093/0869-0189-2012-0-2-102-107
10. Astafyeva N.G., Gamova I.V., Udovichenko E.N., Perfilova I.A. Obesity and bronchial asthma (part 1, 2). Lechashchi vrach Journal 2014; 4-5 (in Russian). Available at: https://www.lvrach.ru
11. Taylor B., Mannino D., Brown C., Crocker D., Twum-Baah N., Holguin F. Body mass index and asthma severity in the National Asthma Survey. Thorax 2008; 63(1):14–20. https://doi:10.1136/thx.2007.082784
12. Ignatova G.L., Makarova E.A. Asthma and obesity: clinical and pathophysiological aspects of new asthma phenotype assignment. Sovremennyye problemy nauki i obrazovaniya =Modern problems of science and education 2016; (4). Available at: http://scienceeducation. ru/ru/article/view?id=25017 (in Russian).
13. Tay T.R., Radhakrishna N., Hore-Lacy F., Smith C., Hoy R., Dabscheck E., Hew M. Comorbidities in difficult asthma are independent risk factors for frequent exacerbations, poor control and diminished quality of life. Respirology 2016; 21(8):1384–1390. https://doi:10.1111/resp.12838
14. Beuther D.A., Weiss S.T., Sutherland E.R. Obesity and asthma. Am. J. Respir. Crit. Care Med. 2006; 174(2):112–119. https://doi:10.1164/rccm.200602-231PP
15. Yubitskaya N.S., Antonyuk M.V. Current issues of non-medicated treatment of patients with bronchial asthma and obesity. Bûlleten' fiziologii i patologii dyhaniâ = Bulletin Physiology and Pathology of Respiration 2019; (73):87–97. https://doi:10.36604/1998-5029-2019-73-87-97 (in Russian).
16. Kim S.H., Sutherland E., Gelfand E. Is there a link between obesity and asthma? Allergy Asthma Immunol. Res. 2014; 6(3):189–195. https://doi:10.4168/aair.2014.6.3.189
17. Sutherland E. R., Goleva E., King T.S., Lehman E., Stevens A.D., Jackson L.P., Stream A.R., Fahy J.V., Leung D.Y.M. Cluster Analysis of Obesity and Asthma Phenotypes. PLoS One 2012; 7(5):e36631. https://doi.org/10.1371/journal.pone.0036631
18. Fomina D.S., Goryachkina L.A., Alekseeva Y.G., Bobrikova E.N. Bronchial asthma and obesity: search for therapeutic models. Pulmonologiya 2014; (6):94–102 (in Russian). https://doi.org/10.18093/0869-0189-2014-0-6-94-102
19. Kosenkova T.V., Novikova V.P. Bronchial asthma and obesity in children. Mechanisms of interrelation. Medicine: theory and practice 2019; 4(1):62–83 (in Russian).
20. Amaral R., Pereira A.M., Jacinto T., Malinovschi A., Janson C., Alving K., Fonseca J.A. Comparison of hypothesis- and data-driven asthma phenotypes in NHANES 2007–2012: the importance of comprehensive data availability. Clin. Transl. Allergy 2019; 9:17. https://doi.org/10.1186/s13601-019-0258-7
21. Chichkova N.V., Gasparyan A.A., Gitel E.P., N.S. Serova, Fomin V.V. Asthma in Overweight and Obese Patients: Assessment of Adipokine Profile with Different Fractions of Adipose Tissue. Practical pulmonology 2019; (3):4–9 (in Russian).
22. Smirnova A.U., Gnoevykh V.V., Portnova J.A. Genetic aspects of multifactorial chronic bronchial obstructive diseases. Ulyanovsk Medico-biological Journal 2014; (1):8–18 (in Russian).
23. Molostova T.N. Genetic Variability of β2 -adrenoreceptors and its Clinical Importance. Practical pulmonology 2017; (2):63–69 (in Russian).
24. Ponomareva M.S., Furman E.G., Khuzina E.A., Yarulina A.M., Zhdanovich E.A. Family polymorphism of ADRB2 gene in childhood bronchial asthma. Perm Medical Journal 2015; 32(5):30–36 (in Russian).
25. Hizawa N. Beta-2 adrenergic receptor genetic polymorphisms and asthma. J. Clin. Pharm. Ther. 2009; 34(6):631–643. https://doi.org/10.1111/j.1365-2710.2009.01066.
26. Fedorova Yu.Yu., Karunas A.S., Murzina R.R., Mukhtarova L.A., Ramazanova N.N., Gimalova G.Ph., Gatiyatullin R.Ph., Zagidullin Sh.Z., Etkina E.I., Khusnutdinova E.K. Association study of the β2 -adrenergic receptor gene polymorphisms with bronchial asthma in Russians. Practical Medicine 2013; (5):116–120 (in Russian).
27. de Paiva A.C.Z., Marson F.A.L., Ribeiro J.D., Bertuzzo C.S. Asthma: Gln27Glu and Arg16Gly polymorphisms of the beta2-adrenergic receptor gene as risk factors. Allergy Asthma Clin. Immunol. 2014; 10(1):8. http://www.aacijournal.com/content/10/1/8
28. March M.E., Sleiman P.M., Hakonarson H. Genetic polymorphisms and associated susceptibility to asthma. Int. J. Gen. Med. 2013; 6:253–265. https://doi.10.2147/IJGM.S28156
29. Holloway J.W., Dunbar P.R., Riley G.A., Sawyer G.M, Fitzharris P.F., Pearce N., Le Gros G.S., Beasley R. Association of beta2-adrenergic receptor polymorphisms with severe asthma. Clin. Exp. Allergy 2000; 30(8):1097–1103. doi: 10.1046/j.1365-2222.2000.00929.x
30. Contopoulos-Ioannidis D.G., Manoli E.N., Ioannidis J.P. Meta-analysis of the association of beta-2-adrenergic receptor polymorphisms with asthma phenotypes. J Allergy Clin. Immunol. 2005; 115(5):963–792. https://doi:10.1016/j.jaci.2004.12.1119
31. Vaskovskiy N.V., Serebrov V.U., Freidin M.B., Ogorodova L.M., Petrovskiy F.I., Deev I.A. Association of β2 -adrenergic receptor polymorphisms with atopic bronchial asthma. Meditsinskaya genetika 2006; 44(2):45–48 (in Russian).
32. D’Amato M., Vitiani L.R., Petrelli G., Ferrigno L., di Pietro A., Trezza R, Matricardi P M Association of persistent bronchial hyperresponsiveness with beta2-adrenoceptor (ADRB2) haplotypes. A population study. Am. J. Respir. Crit. Care Med. 1998; 158(6):1968–1973. https://doi:10.1164/ ajrccm.158.6.9804126
33. Xie H., Cheng Y., Huo Y., Huang G., Su J. Association between b2-Adrenoceptor Gene Polymorphisms and Asthma Risk: An Updated Meta-Analysis. PLoS One 2014; 9(7):e101861. https://doi:10.1371/journal.pone.0101861
34. Liang S.-Q., Chen X.-L., Deng J.-M., Wei X., Gong Ch., Chen Z.-R., Wang Z.-B. Beta-2 Adrenergic Receptor (ADRB2) Gene Polymorphisms and the Risk of Asthma: A Meta-Analysis of Case-Control Studies. PLoS One 2014; 9(8):e104488. https://doi.org/10.1371/journal.pone.0104488
35. Isaza С., Sepúlveda-Arias J.С., Agudelo В.I., Arciniegas W., Henao J., Porras G., Beltra´n L. B2-adrenoreceptor polymorphisms in asthmatic and non-asthmatic schoolchildren from Сolombia and their relationship to treatment response. Pediatr. Pulmonol. 2012; 47(9):848–855. https://doi.org/10.1002/ppul.22521
36. Savelieva O.N., Karunas A.S., Fedorova Yu.Yu., Khunutdinova E.K. The role of B2-adrenergic receptor gene (ADRB2) polymorphisms in asthma. Bashkortostan Medical Journal 2018; 13(5):69–75 (in Russian).
37. Zhao S., Zhang W., Nie X. Association of β2 -adrenergic receptor gene polymorphisms (rs1042713, rs1042714, rs1042711) with asthma risk: a systematic review and updated meta-analysis. BMC Pulm. Med. 2019; 19(1):202. https://doi.org/10.1186/s12890-019-0962-z
38. Chung K.F., Wenzel S.E., Brozek J.L., Bush A., Castro M., Sterk P.J., Adcock I.M., Bateman E.D., Bel E.H., Bleecker E.R., Boulet L.-Ph., Brightling Ch., Chanez P., Dahlen S.-E., Djukanovic R., Frey U., Gaga M., Gibson P., Hamid Q., Jajour N.N., Mauad Th., Sorkness R.L., Teague W.G. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur. Respir. J. 2014; 43(2):343–373. https://doi:10.1183/09031936.00202013
39. Balabolkin I.I., Bulgakova V.A., Pinelis V.G., Tyumentseva E.S. Pharmacogenetics and individualized approach to the therapy of bronchial asthma. Bulletin of Siberian Medicine 2017; 16(2):20–31 (in Russian). https://doi:10.20538/1682-0363-2017-2-20–31
40. 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., Kraft M., Kunselman S.J., Lazarus S.C., Lemanske R.F. Jr., Liggett S.B., Martin R.J., Mitra N., Peters S.P., Silverman E., Sorkness C.A., Szefler S.J., Wechsler M.E., Weiss S.T., Drazen J.M. Use of regularly scheduled albuterol treatment in asthma: genotype-stratified, randomised, placebo-controlled cross-over trial. Lancet 2004; 364(9444):1505–1512. https://doi:10.1016/S0140-6736(04)17273–5
41. Liggett S.B. Polymorphisms of the b2-adrenergic receptor and asthma. Am. J. Respir. Crit. Care Med. 1997; 156(4):156–162. https://doi.org/10.1164/ajrccm.156.4.12tac-15
42. Hall I.P. Genetics and pulmonary medicine: asthma. Thorax 1999; 54(1):65–69. doi: 10.1136/thx.54.1.65 43. Taylor B., Mannino D., Brown C., Crocker D., Twum-Baah N., Holguin F. Body mass index and asthma severity in the National Asthma Survey. Thorax 2008; 63(1):14–20. https://doi:10.1136/thx.2007.082784
43. Blake K., Lima J. Pharmacogenomics of long-acting β2 -agonists. Exp. Opin. Drug Metab. Toxicol. 2015; 11(11):1733–1751. https://doi.org/10.1517/17425255.2015.1071793
44. 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(9):900–905. https://doi:10.3109/02770900903199961
45. Bryantseva O.N., Tikhomirov Ye.Ye, Zhurkova N.V., Voznesenskaya N.I, Bayazutdinova G.M., Averianova N.S., Balabolkin I.I, Pinelis V.G. Polymorphism of the gene of β2 -adrenergic receptor and efficiency of the broncholytic therapy among children with bronchial asthma. Pediatric pharmacology 2007; 4(3):35–39 (in Russian).
46. Bleecker E.R., Postma D.S., Lawrance R.M., Meyers D.A., Ambrose H.J., Goldman M. Effect of ADRB2 polymorphisms on response to longacting β2 -agonist therapy: a pharmacogenetic analysis of two randomised studies. Lancet 2007; 370(9605):2118–2125. https://doi:10.1016/S0140-6736(07)61906-0
47. Slob E.M.A., Vijverberg S.J.H., Palmer C.N.A., Zazuli Z., Farzan N., Oliveri N.M.B., Pijnenburg M.W., Koppelman G.H., Maitland-van der Zee A.H. Pharmacogenetics of inhaled long-acting beta2-agonists in asthma: a systematic review.
48. Pediatr. Allergy Immunol. 2018; 29(7): 705–714. https://doi:10.1111/pai.12956
49. Masuo K., Lambert G.W. Relationships of Adrenoceptor Polymorphisms with Obesity. J. Obes. 2011: 609485. https://doi:10.1155/2011/609485
50. Hupfeld C.J., Dalle S., Olefsky J.M. Beta-Arrestin 1 down-regulation after insulin treatment is associated with supersensitization of beta 2 adrenergic receptor Galpha s signaling in 3T3-L1 adipocytes. Proc. Natl Acad. Sci. USA 2003; 100(1):161–166. https://doi:10.1073/pnas.0235674100
51. Dallongeville J., Helbecque N., Cottel D., Amouyel Ph., Meirhaeghe A. The Gly16-->Arg16 and Gln27-->Glu27 polymorphisms of beta2-adrenergic receptor are associated with metabolic syndrome in men. J. Clin. Endocrinol. Metab. 2003; 88(10):4862–4866. https://doi:10.1210/jc.2003-030173
52. Pereira T.V., Mingroni-Netto R.C., Yamada Y. ADRB2 and LEPR gene polymorphisms: synergistic effects on the risk of obesity in Japanese. Obesity (Silver Spring) 2011; 19(7):1523–1527. https://doi.org/10.1038/oby.2010.322
53. Zhang H., Wu J., Yu L. Association of Gln27Glu and Arg16Gly Polymorphisms in Beta2-Adrenergic Receptor Gene with Obesity Susceptibility: A Meta-Analysis. PLoS One 2014; 9(6):e100489. https://doi:10.1371/journal.pone.0100489
54. Hallstrand T.S., Fisher M.E., Wurfel M.M., Afari N., Buchwald D., Goldberg J. Genetic pleiotropy between asthma and obesity in a community based sample of twins. J. Allergy Clin. Immunol. 2005; 116(6):1235–1241. https://doi:10.1016/j.jaci.2005.09.016
55. Leite N., Lazarotto L., Milano G.E., Kapp Titski A.C., Mühe Consentino C.L., de Mattos F., de Andrade F.A., Furtado-Alle L. Associação do gene ADRB2 com sobrepeso e asma em crianças e adolescentes e sua relação com a aptidão física. Rev. Paul. Pediatr. 2015; 33(4):381–386 (in Portuguese). https://doi.org/10.1016/j.rpped.2015.01.012
56. Evans W., McLeod H.L. Pharmacogenomics-drug disposition, drug targets, and side effects. N. Engl. J. Med. 2003; 348(6):538–549. https://doi:10.1056/NEJMra020526
57. Saint-Pierre P., Bourdin A., Chanez P., Daures J.P., Godard P. Are overweight asthmatics more difficult to control. Allergy 2006; 61(1):79–84. http://dx.doi.org/10.1111/j.1398-9995.2005.00953
58. Yeh K.H., Skowronski M.E., Coreno A.J., Seitz R.E., Villalba K.D., Dickey-White H., McFadden E.R. Impact of obesity on the severity and therapeutic responsiveness of acute episodes of asthma. J. Asthma 2011; 8(6):546–552. http://dx.doi.org/10.3109/02770903.2011.581733
59. Farah C.S., Kermode J.A., Downie S.R., Brown N.J., Hardaker K.M., Berend N., King G.G., Salome C.M. Obesity Is a Determinant of Asthma Control Independent of Inflammation and Lung Mechanics. Chest 2011; 140(3):659–666. https://doi.org/10.1378/chest.11-0027
60. Budchanov Y.I., Delyagin V.M. Genetics of bronchial asthma. Practicheskaya medisina 2010; (6):19–21 (in Russian).
Review
For citations:
Telepneva R.S., Evseeva G.P., Nagovitsina E.B., Suprun S.V., Lebed’ko O.A. ADRB2 gene polymorphism in children with asthma and obesity. Bulletin Physiology and Pathology of Respiration. 2020;(77):87-98. (In Russ.) https://doi.org/10.36604/1998-5029-2020-77-87-98
Views:
476
Email this article 