Genetic markers of children asthma: predisposition to disease course variants

Author:

Smolnikova M. V.1ORCID,Kasparov Ed. W.1ORCID,Malinchik M. A.1ORCID,Kopylova K. V.1ORCID

Affiliation:

1. Scientific Research Institute of Medical Problems of the North – a separate division of the Federal Research Center “Krasnoyarsk Science Center” of the Siberian Branch of the Russian Academy of Sciences

Abstract

Asthma is a heterogeneous and often difficult to treat condition that results in a disproportionate cost to healthcare systems. Children with severe asthma are at increased risk for adverse outcomes including medication-related side effects, life-threatening exacerbations, and impaired quality of life. An important therapeutic focus is to achieve disease control, which is supposed to involve a personalized approach to treatment of asthma of any severity. Asthma is a multifactorial disease with a significant genetic determinant, however, the inheritance of asthma has not been fully elucidated. Polymorphic genes of inflammatory mediators, including cytokines, play an important role in developing various disease forms. In the current study, large-scale original data on the prevalence of cytokine gene genotypes (IL2, IL4, IL5, IL6, IL10, IL12, IL13, IL17A, IL31, IL33, IFNG, TNFA) among Russian children with asthma in Krasnoyarsk region have been obtained. Genotyping was carried out using real-time PCR. We identified markers predisposing to the development of different variants of the course of childhood asthma: the CT genotype and T allele of IL4 rs2243250 are associated with asthma (p < 0.05), especially in mild asthma and in controlled asthma. The TT genotype and allele T of IL13 rs1800925 are associated with severe and uncontrolled asthma (p < 0.05). The AA genotype of IL17A rs2275913, the TT genotype of IFNG rs2069705 and allelic A variants of TNFA rs1800629 are associated with mild asthma, and the TT genotype of IFNG rs2069705 is additionally associated with controlled asthma. The results obtained will supplement information on the prevalence of polymorphic variants of the cytokine genes in the Russian population and in asthma patients with different disease courses, which is likely to be used in order to shape a plan for Public Health Authority to prevent the development of severe uncontrolled asthma and to optimize personalized therapy.

Publisher

Institute of Cytology and Genetics, SB RAS

Subject

General Biochemistry, Genetics and Molecular Biology,General Agricultural and Biological Sciences

Reference27 articles.

1. Chen J., Deng Y., Zhao J., Luo Z., Peng W., Yang J., Ren L., Wang L., Fu Z., Yang X., Liu E. The polymorphism of IL-17 G-152A was associated with childhood asthma and bacterial colonization of the hypopharynx in bronchiolitis. J. Clin. Immunol. 2010;30(4):539-545. DOI 10.1007/S10875-010-9391-8.

2. Chuchalin A.G., Khaltaev N., Antonov N.S., Galkin D.V., Manakov L.G., Antonini P., Murphy M., Solodovnikov A.G., Bousquet J., Pereira M.H.S., Demko I.V. Chronic respiratory diseases and risk factors in 12 regions of the Russian Federation. Int. J. Chron. Obstruct. Pulmon. Dis. 2014;9:963-974. DOI 10.2147/COPD.S67283.

3. Espinoza J.L., Takami A., Nakata K., Onizuka M., Kawase T., Akiyama H., Miyamura K., Morishima Y., Fukuda T., Kodera Y., Nakao S. A genetic variant in the IL-17 promoter is functionally associated with acute graft-versus-host disease after unrelated bone marrow transplantation. PloS One. 2011;6(10):e26229. DOI 10.1371/JOURNAL.PONE.0026229.

4. GBD 2015 Chronic Respiratory Disease Collaborators. Global, regional, and national deaths, prevalence, disability-adjusted life years, and years lived with disability for chronic obstructive pulmonary disease and asthma, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet Respir. Med. 2017;5(9):691-706. DOI 10.1016/S2213-2600(17)30293-X.

5. Hancox R.J., Cowan D.C., Aldridge R.E., Cowan J.O., Palmay R., Williamson A., Town G.I., Taylor D.R. Asthma phenotypes: Consistency of classification using induced sputum. Respirology. 2012;17(3):461-466. DOI 10.1111/J.1440-1843.2011.02113.X.

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