Preview

Tuberculosis and Lung Diseases

Advanced search

Polymorphism of genes of Toll-like receptors as a potential factor of predisposition to tuberculosis

https://doi.org/10.21292/2075-1230-2018-96-9-11-16

Abstract

The objective of the study: to detect genotypes and frequency of gene alleles of Toll-receptors (Arg753Gln – for TLR2; Phe412Leu – for TLR3; Asp299Gly – for TLR4; Ser249Pro – for TLR6) among respiratory tuberculosis patients in Zabaykalsky Kray.

Subjects and methods. The distribution of genotypes of allele variants of Toll-receptors genes was analyzed in 120 respiratory tuberculosis patients and 30 healthy volunteers with a compatible gender and age distribution. Genomic DNA was isolated from leukocytes of the whole blood. In order to detect polymorphic variants of Toll-receptors genes, real-time PCR was used. The distribution of genotypes as per investigated polymorphic loci was tested for relevance using Hardy – Weinberg equilibrium. The frequency of genotype distribution in the groups was compared by Pearson's chi-square test with Yates's correction for continuity using 4-field contingency tables. The decision of the association between genotypes and the disease was made based on the value of the odds ratio with 95% of confidence intervals. Additionally, to confirm and analyze the correlation force of genotypes and development of tuberculosis based on the principle of mutual contingency, φ test (Kramer test, Chuprov test) was calculated.

Results. Polymorphism of TLR2, TLR3 and TLR6 genes predispose the development of tuberculosis. The following genotypes make the biggest contribution to the formation of predisposition to tuberculosis: Asp/Asp genotype of TLR4 gene (Asp299Gly), Ser/Ser polymorphism of TLR6 gene (Ser249Pro), heterozygous Asp/Gly of TLR4 gene (Asp299Gly) and mutation Pro/Pro polymorphism of TLR6 gene (Ser249Pro). The protective effect against the development of tuberculosis is related to carriage of homozygous Arg/Arg genotype of TLR2 polymorphism, homozygous Phe/Phe genotype of TLR3 gene and heterozygous Ser/Pro polymorphism of TLR6 gene.

About the Authors

E. S. Bogodukhovа
Chita State Medical Academy
Russian Federation

Ekaterina S. Bogodukhova - Assistant of Tuberculosis Department.

39a, Gorkogo St., Chita, 672090



E. E. Bаyke
Chita State Medical Academy
Russian Federation

Evgeniy E. Bayke - Candidate of Medical Sciences, Associate Professor, Head of Tuberculosis Department.

39a, Gorkogo St., Chita, 672090



References

1. Bayke E.E., Bogodukhova E.S. The role of gene polymorphism of TOLL-like receptors in the development of tuberculosis (Epub.). ENI Zabaykalskiy Meditsinskiy Vestnik, 2015, no. 2, pp. 167-173. (In Russ.) Available at: http://medacadem. chita.ru/zmv.

2. Gankovskaya O.А., Zverev V.V. Interaction of viruses and Toll-like receptors. Journal Mikrobiologii, Epidemiologii i Immunologii, 2010, no. 2, pp. 101-105. (In Russ.)

3. Zakharova M.V., Stakhanov V.А., Mezentseva M.V. Cytokines in the anti-tuberculosis immunity. Vestnik RUDN, Seriya Meditsina, 2009, no. 4, pp. 297-300. (In Russ.)

4. Ketlinskiy S.А., Simbirtsev А.S. Tsitokiny. [Cytokines]. St. Petersburg, Foliant Publ., 2008, 552 p.

5. Kovalchuk L.V. et al. Receptors of innate immunity: approaches to quantity and functional assessment of human toll-like receptors. Immunologiya, 2008, vol. 29, no. 4, pp. 223-227. (In Russ.)

6. Kovalchuk L.V. The doctrine of inflammation in the light of new data: development of the idea of I.I. Mechnikov. Journal Mikrobiologii, Epidemiologii i Immunologii, 2008, no. 5, pp. 10-15. (In Russ.)

7. Krokhaleva Yu.А., Strambovskaya N.N., Аlferova А.E. Genetic polymorphism of TOLL-like receptors in the patients with ischemic stroke in Zabaykalsky Kray (Epub.). Zabaikalsky Meditsinsky Vestnik, 2014, no. 4, pp. 12-15. (In Russ.) Available at: http://medacadem. chita.ru/zmv.

8. Kubanov А.L. et al. The role of toll-like receptor of type 7 in the development of true oncolytic pemphigus. Tsitokiny i Vospaleniye, 2012, vol. 12, no. 4, pp. 7-14. (In Russ.)

9. Perelman M.I., Bogadelnikova I.V. Ftiziatriya. [Phthisiology]. Moscow, GEOTAR-Media Publ., 2012, 446 p.

10. Petrova E.А., Okhlopkov V.А. Clinical characteristics and predicting the course of psoriasis vulgaris in the patients with polymorphism of genes of toll-receptors of types 4 and 9. About Issues Search Rules, 2013, no. 9, pp. 435-439. (In Russ.)

11. Rider G.L. Epidemiologicheskie osnovy borby s tuberkulezom. [Epidemiological basics of tuberculosis control]. Moscow, 2001, 192 p.

12. Svitich O.A. et al. Association of polymorphic markers localized in 5-untranslated region of β-defensin DEFB1 gene with hypertrophic adenoid vegetation. Vestnik RGDU, 2011, no. 3, pp. 23-25. (In Russ.)

13. Sulskaya Yu.V. Genetic polymorphism of toll-receptors of type 4 in those with type 2 diabetes. Tavricheskiy Mediko-Biologicheskiy Vestnik, 2009, no. 3, pp. 72-74. (In Russ.)

14. Ftiziatriya. Natsionalnoye rukovodstvo. [Phthisiology. National Guidelines]. M.I. Perelman, eds., Moscow, GEOTAR-Media Publ., 2007, 512 p.

15. Khaitov R.M., Paschenkov M.V., Pinegin B.V. The role of pattern recognition receptors in the innate adaptive immunity. Immunologiya, 2009, no. 1, pp. 66-76. (In Russ.)

16. Scheblyakov D.V. et al. Toll-like receptors and their impact on tumor progression, Acta Naturae (Russian version), 2010, vol. 2, no. 3, pp. 28-37. (In Russ.)

17. Yarilin A.A. Immunologiya. [Immunology]. Moscow, GEOTAR-Media Publ., 2010, 562 p.

18. Brightbill H.D. et al. Host defense mechanisms triggered by microbial lipoproteins through toll-like receptor. Science, 1999, vol. 285, no. 5428, pp. 732-736.

19. Drexler S.K., Foxwell B.M. The role of toll-like receptors in chronic inflammation. Int. 3. Biochem. Cell Biol., 2010, vol. 42, no. 4, pp. 506-518.

20. Kawai T., Akira S. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat. Immunol., 2010, vol. 11, no. 5, pp. 373-384.

21. Medzhitov R. Toll-like receptors and innate immunity. Nature Reviews Immunology, 2001, pp. 135-145.

22. Miller L.S. Toll-like receptors in skin. Adv. Dermatol., 2008, vol. 24, pp. 71-87.

23. O'Nail L.A. Toll-like receptorsin inflammation. Basel: Birkhauser Verlag. 2005, 244 p.

24. Takeda K., Akira S. Toll-receptors in innate immunity. Intern. Immunology, 2005, vol. 7, no. 1, pp. 1-14.

25. Takeda K., Kaisho T., Akira S. Toll-like receptors. Ann. Rev. Immunol., 2003, vol. 21, pp. 335-376.


Review

For citations:


Bogodukhovа E.S., Bаyke E.E. Polymorphism of genes of Toll-like receptors as a potential factor of predisposition to tuberculosis. Tuberculosis and Lung Diseases. 2018;96(9):11-16. (In Russ.) https://doi.org/10.21292/2075-1230-2018-96-9-11-16

Views: 1145


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 2075-1230 (Print)
ISSN 2542-1506 (Online)