Effect of TRPA1 gene polymorphisms on predisposition to the formation of bronchial asthma
https://doi.org/10.36604/1998-5029-2019-73-27-33
Abstract
Introduction. The results of studies conducted in recent years in the area of the functional role and structural features of transient receptor potential (TRP) channels increasingly indicate their involvement in the pathogenesis of various diseases of the respiratory tract, such as asthma and chronic obstructive pulmonary disease. In particular, TRPA1 has repeatedly been studied in asthma and asthma-associated phenomena in vivo and in vitro. It is important to note that some researchers have found a significant effect of certain genetic features of this channel on the formation of various pathological conditions in humans.
Aim. The purpose of this study was to examine the possible relationship of TRPA1 polymorphisms with a predisposition to the formation of asthma in adults.
Materials and methods. A total of 512 subjects were included in the study, among them 427 patients with asthma and 85 people with chronic non-obstructive bronchitis. Eight single nucleotide polymorphisms (SNPs) of TRPA1 gene were genotyped by LATE-PCR method. Results. As a result of the associative analysis, the relationship of SNPs rs6996723 with asthma in adults was established. CC and CT genotypes prevailed in patients with asthma, while homozygous TT genotype, on the contrary, was more frequently observed in the control group as compared with asthmatics. The differences in the frequencies of genotypes were significant in the following genetic models: multiplicative (OR 1.68 95% CI [1.13-2.49], p=0.01), general (p=0.004), additive (p=0.01) and dominant (OR 4.10 95%CI [1.67-10.06], p=0.001).
Conclusion. Thus, it can be concluded that the presence of C allele for rs6996723 predisposes to a higher risk of asthma development among persons aged over 18 years. In case of additional verification of the results, the data on the presence of a specific allelic variant of rs6996723 SNP can be used to individually predict the risk of asthma development.
About the Authors
O. O. Kotova
Far Eastern Scientific Center of Physiology and Pathology of Respiration
Russian Federation
Russian Federation
Olesya O. Kotova - MD, Postgraduate Student, Laboratory of Molecular and Translational Research.
22 Kalinina Str., Blagoveshchensk, 675000
D. A. Gassan
Far Eastern Scientific Center of Physiology and Pathology of Respiration
Russian Federation
Russian Federation
Dina A. Gassan - MD, Postgraduate Student, Laboratory of Molecular and Translational Research.
22 Kalinina Str., Blagoveshchensk, 675000
D. E. Naumov
Far Eastern Scientific Center of Physiology and Pathology of Respiration
Russian Federation
Russian Federation
Denis E. Naumov - MD, PhD (Med.), Head of Laboratory of Molecular and Translational Research.
22 Kalinina Str., Blagoveshchensk, 675000
E. G. Sheludko
Far Eastern Scientific Center of Physiology and Pathology of Respiration
Russian Federation
Russian Federation
Elizaveta G. Sheludko - MD, Junior Staff Scientist, Laboratory of Molecular and Translational Research.
22 Kalinina Str., Blagoveshchensk, 675000
References
1. Bautista D.M., Pellegrino M., Tsunozaki M. TRPA1: A gatekeeper for inflammation. Annu. Rev. Physiol. 2013; 75:181-200. doi: 10.1146/annurev-physiol-030212-183811
2. Benemei S., Fusi C., Trevisan G., Geppetti P. The TRPA1 channel in migraine mechanism and treatment. Br. J. Pharmacol. 2014; 171(10):2552-2567. doi: 10.nn/bph.12512
3. Gallo V, Dijk F.N., Holloway J.W., Ring S.M., Koppelman G.H., Postma D.S., Strachan D.P., Granell R., de Jongste J.C., Jaddoe V.W., den Dekker H.T., Duijts L, Henderson A.J., Shaheen S.O. TRPA1 gene polymorphisms and childhood asthma. Pediatr. Allergy Immunol. 2017; 28(2):191-198. doi: 10.1in/pai.12673
4. Julius D. TRP channels and pain. Annu. Rev. Cell. Dev. Biol. 2013; 29:355-84. doi: 10.n46/annurev-cellbio-101011-155833
5. Nassini R., Pedretti P., Moretto N., Fusi C., Carnini C., Facchinetti F., Viscomi A.R., Pisano A.R., Stokesbeny S., Brunmark C., Svitacheva N., McGarvey L., Patacchini R., Damholt A.B., Geppetti P., Materazzi S. Transient receptor potential ankyrin 1 channel localized to non-neuronal airway cells promotes non-neurogenic inflammation. PLoS One 2012; 7(8):e42454. doi: 10.1371/journal.pone.0042454
6. Nilius B., Appendino G., Owsianik G. The transient receptor potential channel TRPA1: from gene to pathophysiology. Pflug. Arch. 2012; 464(5):425-58. doi: 10.1007/s00424-012-n58-z
7. Sawada Y., Hosokawa H., Matsumura K., Kobayashi S. Activation of transient receptor potential ankyrin 1 by hydrogen peroxide. Eur. J. Neurosci. 2008; 27(5):1131-1142. doi: 10.1111/j.1460-9568.2008.06093.x
8. Schulze A., Hartung P., Schaefer M., Hill K. Transient receptor potential ankyrin 1 (TRPA1) channel activation by the thienopyridine-type drugs ticlopidine, clopidogrel, and prasugrel. Cell Calcium 2014; 55(4):200-207. doi: 10.1016/j.ceca.2014.02.014
9. Smit L.A., Kogevinas M., Anto J.M., Bouzigon E., Gonzalez J.R., Le Moual N., Kromhout H., Carsin A.E., Pin I., Jarvis D., Vermeulen R., Janson C., Heinrich J., Gut I., Lathrop M., Valverde M.A., Demenais F., Kauffmann F. Transient receptor potential genes, smoking, occupational exposures and cough in adults. Respir. Res. 2012; 13(1):26. doi: 10.1186/1465-9921-13-26
10. Taylor-Clark T.E., Ghatta S., Bettner W., Undem B.J. Nitrooleic Acid, an Endogenous Product of nitrative stress, activates nociceptive sensory nerves via the direct activation of TRPA1. Mol. Pharmacol. 2009; 75(4):820-829. doi: 10.1124/mol.108.054445
11. Trevisani M., Siemens J., Materazzi S., Bautista D.M., Nassini R., Campi B., Imamachi N., Andre E., Patacchini R., Cottrell G.S., Gatti R., Basbaum A.I., Bunnett N.W., Julius D., Geppetti P. 4-Hydroxynonenal, an endogenous aldehyde, causes pain and neurogenic inflammation through activation of the irritant receptor TRPA1. Proc. Natl. Acad. Sci. USA 2007; 104(33): 13519-13524. doi: 10.1073/pnas.0705923104
12. World Health Organization. Chronic respiratory diseases. [March 21, 2019]. Available at: https://www.who.int/res-piratory/en/
Review
For citations:
Kotova O.O., Gassan D.A., Naumov D.E., Sheludko E.G. Effect of TRPA1 gene polymorphisms on predisposition to the formation of bronchial asthma. Bulletin Physiology and Pathology of Respiration. 2019;(73):27-33. (In Russ.) https://doi.org/10.36604/1998-5029-2019-73-27-33
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