Optimization of bronchial asthma treatment according to polymorphism in the leukotriene-C4 synthase gene
DOI:
https://doi.org/10.15587/2519-4798.2021.232971Keywords:
bronchial asthma, -444C-polymorphism of the LTC4-S gene, genotype, aspirin asthma, antileukotriene therapy, inhaled corticosteroidsAbstract
The aim of the study was to investigate the effectiveness of different schemes of basic asthma therapy depending on the polymorphism of the LTC4 gene.
Materials and methods. 181 patients with asthma were recruited to participate in the study. All patients included in the study underwent a general clinical study, spirometry, the level of asthma control was determined by Asthma control questionnaire 5 (ACQ-5), by studying the polymorphism of the LTC4 gene, it was determined that patients belong to the A/A, A/C and C/C genotypes.
Results. Allelic -444C polymorphism of the LTC4-S gene (rs 730012) had the following genotype frequency among asthma patients: A/A – 77 people (42.6 %), A/C – 73 people (40.3 %) and C/C – 31 people (17.1 %).
In groups of patients with genotypes A/A and A/C, during treatment with a low dose of ICS and montelukast, there was a significant improvement in FEV1 and the score according to the ACQ-5 questionnaire (asthma control level). However, in the group of patients with the C/C genotype, there were no significant changes in FEV1 and the score according to the ACQ-5 questionnaire.
In the groups of patients with genotypes A/A and C/C on the background of increasing the dose of ICS to medium in a fixed combination with LABA compared with the results of treatment with low-dose ICS and montelukast, there was a significant improvement in FEV1 and asthma control – ACQ- 5. At the same time, in the group of patients with genotype A/C, there were no reliable indicators of FEV1 and ACQ-5 score changes.
Conclusions. The frequency of genotypes A/A, A/C and C/C for LTC4S polymorphism in the studied population are 42.6 %, 40.3 % and 17.1 %, respectively.
Patients with genotypes A/A and C/C have a significant response to treatment with a low dose of ICS and montelukast in the form of an improvement in FEV1 and ACQ-5 score.
Increasing the dose of ICS up to moderate in a fixed combination with β2-LABA in groups of patients with genotypes A/A and C/C leads to a significant improvement in the FEV1, as well as in the asthma control level - ACQ-5
References
- Global initiative for asthma (2017). Available at: https://ginasthma.org/ Last accessed: 13.04.2021
- Jones, T. L., Neville, D. M., Chauhan, A. J. (2018). Diagnosis and treatment of severe asthma: a phenotype-based approach. Clinical Medicine, 18 (Suppl 2), s36–s40. doi: http://doi.org/10.7861/clinmedicine.18-2-s36
- Sanak, M., Pierzchalska, M., Bazan-Socha, S., Szczeklik, A. (2000). Enhanced Expression of the Leukotriene C4Synthase Due to Overactive Transcription of an Allelic Variant Associated with Aspirin-Intolerant Asthma. American Journal of Respiratory Cell and Molecular Biology, 23 (3), 290–296. doi: http://doi.org/10.1165/ajrcmb.23.3.4051
- Kedda, M.-A., Shi, J., Duffy, D., Phelps, S., Yang, I., O’Hara, K. et. al. (2004). Characterization of two polymorphisms in the leukotriene C4 synthase gene in an Australian population of subjects with mild, moderate, and severe asthma. Journal of Allergy and Clinical Immunology, 113 (5), 889–895. doi: http://doi.org/10.1016/j.jaci.2004.02.008
- Sampson, A. P., Cowburn, A. S., Sladek, K., Adamek, L., Nizankowska, E., Szczeklik, A. et. al. (1997). Profound Overexpression of Leukotriene C4 Synthase in Bronchial Biopsies from Aspirin-Intolerant Asthmatic Patients. International Archives of Allergy and Immunology, 113 (1-3), 355–357. doi: http://doi.org/10.1159/000237600
- Woo, S.-D., Luu, Q. Q., Park, H.-S. (2020). NSAID-Exacerbated Respiratory Disease (NERD): From Pathogenesis to Improved Care. Frontiers in Pharmacology, 11. doi: http://doi.org/10.3389/fphar.2020.01147
- Acq5. Available at: https://www.respirologist.com.au/acq5/ Last accessed: 22.04.2021
- Kang, M.-J., Kwon, J.-W., Kim, B.-J., Yu, J., Choi, W.-A., Shin, Y.-J., Hong, S.-J. (2011). Polymorphisms of the PTGDR and LTC4S influence responsiveness to leukotriene receptor antagonists in Korean children with asthma. Journal of Human Genetics, 56 (4), 284–289. doi: http://doi.org/10.1038/jhg.2011.3
- Thompson, M. D., Capra, V., Clunes, M. T., Rovati, G. E., Stankova, J., Maj, M. C., Duffy, D. A. (2016). Cysteinyl Leukotrienes Pathway Genes, Atopic Asthma and Drug Response: From Population Isolates to Large Genome-Wide Association Studies. Frontiers in Pharmacology, 7. doi: http://doi.org/10.3389/fphar.2016.00299
- Zhang, Y., Huang, H., Huang, J., Xiang, Z., Yang, M., Tian, C., Fan, H. (2012). The −444A/C Polymorphism in the LTC4S Gene and the Risk of Asthma: A Meta-analysis. Archives of Medical Research, 43 (6), 444–450. doi: http://doi.org/10.1016/j.arcmed.2012.08.003
- Berghea, E. C., Popa, L. O., Dutescu, M. I. (2015). Association of Leukotriene C4 Synthase A-444C Polymorphism with Asthma and Asthma Phenotypes in Romanian Population. Maedica, 10 (2), 91–96.
- Lima, J. J., Zhang, S., Grant, A., Shao, L., Tantisira, K. G., Allayee, H. et. al. (2006). Influence of Leukotriene Pathway Polymorphisms on Response to Montelukast in Asthma. American Journal of Respiratory and Critical Care Medicine, 173 (4), 379–385. doi: http://doi.org/10.1164/rccm.200509-1412oc
- Quintero, I. Q., de Sanctis, J., Garmendia, J., Mestre, M. F., Moreno, D. (2012). 336 The Leukotriene C4 Synthase (A-444C) Promoter Polymorphism in Venezuelan Individuals with Asthma. World Allergy Organization Journal, 5, S108. doi: http://doi.org/10.1097/01.wox.0000412099.33967.78
- Cai, C., Zhou, M. X., Li, Y. P., Chen, C. S. (2011). Zhonghua jie he he hu xi za zhi. Chinese journal of tuberculosis and respiratory diseases, 34 (5), 362–366.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2021 Nataliia Cherednichenko, Maryna Kochuieva, Hanna Tymchenko, Yulia Zaikina, Gennadii Kochuiev, Andrii Liashok
This work is licensed under a Creative Commons Attribution 4.0 International License.
Our journal abides by the Creative Commons CC BY copyright rights and permissions for open access journals.
Authors, who are published in this journal, agree to the following conditions:
1. The authors reserve the right to authorship of the work and pass the first publication right of this work to the journal under the terms of a Creative Commons CC BY, which allows others to freely distribute the published research with the obligatory reference to the authors of the original work and the first publication of the work in this journal.
2. The authors have the right to conclude separate supplement agreements that relate to non-exclusive work distribution in the form in which it has been published by the journal (for example, to upload the work to the online storage of the journal or publish it as part of a monograph), provided that the reference to the first publication of the work in this journal is included.