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Association of CYP3A5 (6986A>G) gene polymorphism with the effectiveness of anti-inflammatory therapy in children with bronchial asthma

https://doi.org/10.21508/1027-4065-2019-64-3-73-77

Abstract

Inhaled glucocorticosteroids are the main drugs used to control bronchial asthma in children. P450-cytochrome of  3A (CYP3A) family is involved in  their metabolism. CYP3A5-isoenzyme plays the leading role in  the respiratory tract. We described 6986A>G polymorphism in the CYP3A5 gene encoding this isoenzyme.

Aim of the study. To evaluate the association of CYP3A5 (6986A> G) gene polymorphism with the effectiveness of drugs in children with bronchial asthma.

Materials and methods. We examined 108 children from 6 to 17 years with bronchial asthma. The allergist carried out the dynamic outpatient polyclinic follow-up of patients, assessed the symptoms of the disease and corrected the corresponding basic therapy. All children underwent genotyping for the 6986A> G polymorphic marker of the CYP3A5 gene.

Results. Ten (9.26%) children were heterozygous for the 6986A> G polymorphic marker of  the CYP3A5 gene (AG genotype). The authors obtained statistically significant differences in the frequency of the AG genotype between the patients receiving control therapy for bronchial asthma of the 1st – 2nd stage and the patients with control therapy of the 3rd and higher stages in accordance with GINA criteria (p=0.031). In the group with severe bronchial asthma, the number of heterozygotes for the 6986A> G polymorphic marker of the CYP3A5 gene was significantly higher than among children with a mild course of the disease (p=0.029).

Conclusion. The AG genotype and A-allele (CYP3A5 gene, A6986A> G polymorphism) are associated with the need for greater volume of control therapy for bronchial asthma and they are risk factors of a more severe course of the disease.

About the Authors

A. K. Zastrozhina
Children’s State Polyclinic No.42
Russian Federation


I. N. Zakharova
Russian Medical Academy of Continuing Education
Russian Federation


D. A. Sychev
Russian Medical Academy of Continuing Education
Russian Federation


E. A. Grishina
Russian Medical Academy of Continuing Education
Russian Federation


K. A. Ryzhikova
Russian Medical Academy of Continuing Education
Russian Federation


References

1. Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention. 2018; http://www.ginasthma.org/

2. Национальная программа «Бронхиальная астма у детей. Стратегия лечения и профилактика». 5-е изд., перераб. и доп. М.: Оригинал-макет, 2017; 160 [National program “Bronchial asthma in children. Treatment strategy and prevention. 5th revised and enlarged edition. M.: Original-maket, 2017; 160. (in Russ)]

3. Клинические рекомендации «Бронхиальная астма у детей» // https://www.pediatr-russia.ru/sites/default/files/ file/kr_bronhast.pdf [Clinical recommendations «Bronchial asthma in children» // https://www.pediatr-russia.ru/sites/ default/files/file/kr_bronhast.pdf (in Russ)]

4. Murai T., Reilly C.A., Ward R.M., Yost G.S. The inhaled glucocorticoid fluticasone propionate efficiently inactivates cytochrome P450 3A5, a predominant lung P450 enzyme. Chem Res Toxicol 2010; 23: 1356–1364. DOI: 10.1021/tx100124k

5. Пономаренко Т.М., Сычев Д.А., Чикало А.О., Бердникова Н.Г., Кукес В.Г. Система цитохрома Р450 в легких: роль в патогенезе заболеваний и фармакокинетике лекарственных средств. Фармакокинетика ифармакодинамика 2012; 1(4): 25–28. [PonomarenkoT.M., Sychov D.A., Chikalo A.O., Berdnikova N.G., Kukes V.G. Cytochrome P450 system in the lungs: role in the pathogenesis of diseases and pharmacokinetics of drugs. Pharmacokinetics and Pharmacodynamics 2012; 1(4): 25–28. (in Russ)]

6. Застрожина А.К., Сычев Д.А. Фармакогенетические аспекты эффективности и безопасности ингаляционных глюкокортикостероидов в лечении бронхиальной астмы. Клиническая фармакология и терапия 2018; 27(4): 64–68. [Zastrozhina A.K., Sychev D.A. Pharmacogenetic aspects of the efficacy and safety of inhaled glucocorticosteroids in bronchial asthma. Klinicheskaya farmakologiya i terapiya 2018; 27(4): 64– 68. DOI: 10.32756/0869-5490-2018-5-64-68. (in Russ)]

7. Daley Yates P.T., Price A.C., Sisson J.R., Pereira A., Dallow N. Beclomethasone dipropionate: absolute bioavailability, pharmacokinetics and metabolism following intravenous, oral, intranasal and inhaled administration in men. Br J Clin Pharmacol 2001; 51(5): 400–409. DOI: 10.1046/j.0306- 5251.2001.01374.x

8. Quaranta S., Chevalier D., Allorfe D., Lo-Guidice J.M., MigotNabias F., Kenani A. et al. Ethnic differences in the distribution of CYP3A5 gene polymorphisms. Xenobiotica 2006; 36: 1191–2000. DOI: 10.1080/00498250600944300

9. Thum T., Erpenbeck V.J., Moeller J., Hohlfeld J.M., Krug N., Borlak J. Expression of Xenobiotic Metabolizing Enzymes in Different Lung Compartments of Smokers and Nonsmokers. Environ Health Perspect 2006; 114(11): 1655–1661. DOI: 10.1289/ehp.8861

10. Seo T., Pahwa P., McDuffie H., Yurube K., Egoshi M., Umemoto Y. et al. Association between cytochrome P450 3A5 polymorphism and the lung function in Saskatchewan grain workers. Pharmacogenet Genomics 2008; 18(6): 487–493. DOI: 10.1097/FPC.0b013e3282fb02ba

11. Stockmann C., Fassl B., Gaedigk R., Nkoy F., Uchida D.A., Monson S. et al. Fluticasone propionate pharmacogenetics: CYP3A4*22 polymorphism and pediatric asthma control. J Pediatr 2013; 162: 1222–1227, e1-2. DOI: 10.1016/j. jpeds.2012.11.031

12. Stockmann C., Reilly C.A., Fassl B., Gaedigk R., Nkoy F., Stone B. et al. Effect of CYP3A5*3 on asthma control among children treated with inhaled beclomethasone. J Allergy Clin Immunol 2015; 136(2): 505–507. DOI: 10.1016/j. jaci.2015.02.009

13. Juniper E.F., Gruffydd-Jones K., Ward S., Svensson K. Asthma Control Questionnaire in children: validation, measurement properties, interpretation. Eur Respir J 2010; 36: 1410–1416. DOI: 10.1183/09031936.00117509

14. Nathan R.A., Sorkness C.A., Kosinski M., Schatz M., Li J.T., Marcus P. et al. Development of the asthma control test: a survey for assessing asthma control. J Allergy Clin Immunol 2004; 113: 59–65. DOI: 10.1016/j.jaci.2003.09.008

15. Liu A.H., Zeiger R., Sorkness C., Mahr T., Ostrom N., Burgess S. et al. Development and cross-sectional validation of the Childhood Asthma Control Test. J Allergy Clin Immunol 2007; 119: 817–825. DOI: 10.1016/j.jaci.2006.12.662


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For citations:


Zastrozhina A.K., Zakharova I.N., Sychev D.A., Grishina E.A., Ryzhikova K.A. Association of CYP3A5 (6986A>G) gene polymorphism with the effectiveness of anti-inflammatory therapy in children with bronchial asthma. Rossiyskiy Vestnik Perinatologii i Pediatrii (Russian Bulletin of Perinatology and Pediatrics). 2019;64(3):73-77. (In Russ.) https://doi.org/10.21508/1027-4065-2019-64-3-73-77

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ISSN 1027-4065 (Print)
ISSN 2500-2228 (Online)