Skip to main content
SpringerLink
Log in

Association between Allelic Variants of the Genes Involved in Glucocorticoids Metabolism and Asthma

  • HUMAN GENETICS
  • Published:
Russian Journal of Genetics Aims and scope Submit manuscript

Abstract

Bronchial asthma (BA) is a common severe and disabling multifactorial disease. Up to 50–60% of differences in sensitivity to therapy in patients with BA is due to genetic variability. We studied polymorphic variants of four genes involved in the metabolism of glucocorticosteroids in patients with asthma and healthy individuals of Russian, Tatar and Bashkir ethnic origin: rs37973 of the glucocorticoid-induced transcript 1 gene (GLCCI1), rs2305089 of the transcription factor T gene (TBXT), rs10044254 of the F-box and leucine-rich repeat protein gene (FBXL7), rs11123610 of the allantoicase gene (ALLC). It has been established that, in Tatars, the rs37973 G allele of the GLCCI1 gene is a marker of an increased risk of developing BA with an uncontrolled course, while a decrease in spirography is observed in patients with the rs37973 AG and rs37973 GG genotypes of the GLCCI1 gene compared with children with rs37973 AA genotypes. In Bashkirs, a marker of an increased risk of developing the disease is the rs2305089 T allele of the TBXT gene polymorphic variant.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

REFERENCES

  1. Global Initiative for Asthma, Global strategy for asthma management and prevention, updated 2018, Vancouver: GINA, 2018. https://ginasthma.org/2018-gina-report-global-strategy-for-asthma-management-and-prevention/.

  2. Isidoro-García, M., Sánchez-Martín, A., García-Sánchez, A., et al., Pharmacogenetics and the treatment of asthma, Pharmacogenomics, 2017, vol. 18, no. 13, pp. 1271—1280. https://doi.org/10.2217/pgs-2017-0024

    Article  CAS  PubMed  Google Scholar 

  3. Fedorova, Yu.Yu., Karunas, A.S., Murzina, R.R., et al., Study of the role of polymorphic variants of genes responsible for glucocorticosteroid metabolism in the development of bronchial asthma, Med. Genet., 2016, vol. 15, no. 1, pp. 27—37. https://doi.org/10.1234/XXXX-XXXX-2016-1-27-36

    Article  Google Scholar 

  4. Farzan, N., Vijverberg, S.J., Arets, H.G., et al., Pharmacogenomics of inhaled corticosteroids and leukotriene modifiers: a systematic review, Clin. Exp. Allergy, 2017, vol. 47, no. 2, pp. 271—293. https://doi.org/10.1111/cea.12844

    Article  CAS  PubMed  Google Scholar 

  5. Willis-Owen, S.A.G., Cookson, W.O.C., and Moffatt, M.F., The genetics and genomics of asthma, Annu. Rev. Genomics Hum. Genet., 2018, vol. 19, pp. 223—246. https://doi.org/10.1146/annurev-genom-083117-021651

    Article  CAS  PubMed  Google Scholar 

  6. Karunas, A.S., Yunusbaev, B.B., Fedorova, Yu.Yu., et al., Genome-wide association study of bronchial asthma in the Volga—Urals region of Russia, Mol. Biol. (Moscow), 2011, vol. 45, no. 6, pp. 911—920. https://doi.org/10.1134/S0026893311060057

    Article  CAS  Google Scholar 

  7. Karunas, A.S., Yunusbaev, B.B., Fedorova, Yu.Yu., et al., Association of MUC19 gene polymorphic variants with asthma in Russians based on genome-wide study results, Russ. J. Genet., 2015, vol. 51, no. 11, pp. 1135—1143. https://doi.org/10.1134/S1022795415110083

    Article  CAS  Google Scholar 

  8. Tantisira, K.G., Lasky-Su, J., Harada, M., et al., Genome-wide association between GLCCI1 and response to glucocorticoid therapy in asthma, N. Engl. J. Med., 2011, vol. 365, no. 13, pp. 1173—1183.

    Article  CAS  Google Scholar 

  9. Tantisira, K.G., Damask, A., Szefler, S.J., et al., Genome-wide association identifies the T gene as a novel asthma pharmacogenetic locus, Am. J. Respir. Crit. Care Med., 2012, vol. 185, no. 12, pp. 1286—1291. https://doi.org/10.1164/rccm.201111-2061OC

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Park, H.-W., Dahlin, A., Tse, S., et al., Genetic predictors associated with improvement of asthma symptoms in response to inhaled corticosteroids, J. Allergy Clin. Immunol., 2014, vol. 133, no. 3, pp. 664—669. https://doi.org/10.1016/j.jaci.2013.12.1042

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Park, T.-J., Park, J.-S., Cheong, H.S., et al., Genome-wide association study identifies ALLC polymorphisms correlated with FEV1 change by corticosteroid, Clin. Chim. Acta., 2014, vol. 436, pp. 20—26. https://doi.org/10.1016/j.cca.2014.04.023

    Article  CAS  PubMed  Google Scholar 

  12. Natsional’naya programma “Bronkhial’naya astma u detei: strategiya lecheniya i profilaktika” (National Program “Bronchial Asthma in Children: Treatment Strategy and Prevention”), Chuchalin, A.G., Ed., Moscow: Atmosfera, 2008.

    Google Scholar 

  13. Clement, R.F. and Zilber, H.A., Funktsional’no-diagnosticheskie issledovaniya v pul’monologii: metodicheskie rekomendatsii (Functional Diagnostic Tests in Pulmonology: Guidelines), St. Petersburg, 1993.

  14. Mathew, C.C., The isolation of high molecular weight eukaryotic DNA, Methods Mol. Med., 1984, pp. 31—34.

  15. Solé, X., Guinó, E., Valls, J., et al., SNPStats: a web tool for the analysis of association studies, Bioinformatics, 2006, vol. 22, no. 15, pp. 1928—1929.

    Article  Google Scholar 

  16. Hosking, L., Bleecker, E., Ghosh, S., et al., GLCCI1 rs37973 does not influence treatment response to inhaled corticosteroids in white asthma subjects, J. Allergy Clin. Immunol., 2014, vol. 133, no. 2, pp. 587—589. https://doi.org/10.1016/j.jaci.2013.08.024

    Article  CAS  PubMed  Google Scholar 

  17. Vijverberg, S.J., Tavendale, R., Leusink, M., et al., Pharmacogenetic analysis of GLCCI1 in three north European pediatric asthma populations with a reported use of inhaled corticosteroids, Pharmacogenomics, 2014, vol. 15, no. 6, pp. 799—806. https://doi.org/10.2217/pgs.14.37

    Article  CAS  PubMed  Google Scholar 

  18. Izuhara, Y., Matsumoto, H., Kanemitsu, Y., et al., GLCCI1 variant accelerates pulmonary function decline in patients with asthma receiving inhaled corticosteroids, Allergy, 2014, vol. 69, no. 5, pp. 668—673. https://doi.org/10.1111/all.12400

    Article  CAS  PubMed  Google Scholar 

  19. Keskin, O., Uluca, U., Birben, E., et al., Genetic associations of the response to inhaled corticosteroids in children during an asthma exacerbation, Pediatr. Allergy Immunol., 2016, vol. 27, no. 5, pp. 507—513. https://doi.org/10.1111/pai.12566

    Article  PubMed  Google Scholar 

Download references

Funding

The present study was supported by the Ministry of Education and Science of the Russian Federation (state contract no. АААА-А16-116020350032-1) and partially supported by the Russian Foundation for Basic Research (project no. 17-04-02195). DNA samples used in the study were provided by the Institute of Biochemistry and Genetics, Ufa Federal Research Centre, Russian Academy of Sciences, from the “Collection of Human Biological Materials,” supported by the Federal Agency for Scientific Organizations for support of bioresource collections (project no. 007-030164/2).

Author information

Authors and Affiliations

  1. Institute of Biochemistry and Genetics, Ufa Federal Research Centre, Russian Academy of Sciences, 450054, Ufa, Russia

    Yu. Yu. Fedorova, A. S. Karunas, G. F. Gimalova & E. K. Khusnutdinova

  2. Bashkir State University, 450076, Ufa, Russia

    O. N. Savelieva

  3. Bashkir State Medical University, 450000, Ufa, Russia

    A. S. Karunas, R. R. Murzina, R. F. Gatiyatullin, E. I. Etkina & E. K. Khusnutdinova

Authors
  1. Yu. Yu. Fedorova
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. S. Karunas
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. R. R. Murzina
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. O. N. Savelieva
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. G. F. Gimalova
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. R. F. Gatiyatullin
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. E. I. Etkina
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. E. K. Khusnutdinova
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Yu. Yu. Fedorova or A. S. Karunas.

Ethics declarations

Conflicts of interest. The authors declare no conflict of interest.

Statement of compliance with standards of research involving humans as subjects. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants involved in the study.

Additional information

Translated by A. Kazantseva

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fedorova, Y.Y., Karunas, A.S., Murzina, R.R. et al. Association between Allelic Variants of the Genes Involved in Glucocorticoids Metabolism and Asthma. Russ J Genet 55, 1520–1527 (2019). https://doi.org/10.1134/S1022795419120044

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S1022795419120044

Keywords:

Search

Navigation