The Correlation between Single-Nucleotide Polymorphisms in Genes of Lysosomal and Proteasomal Proteolysis and Their Impact on the Effectiveness of Asthma Treatment in Children

O.V. Iemets

Abstract


Purpose. To detect the correlation between single-nucleotide polymorphisms rs510432 in gene ATG5 and rs4769628 in gene POMP, to determine combination of allelic variations at high risk of atopic diseases. To evaluate the impact of allelic variations of above-mentioned gene on the effectiveness of bronchial asthma treatment in children. Materials and methods. To determine the correlation between single-nucleotide polymorphisms in gene ATG5 and РОМР, we have used the method of multifactor dimensionality reduction. To assess the effectiveness of asthma therapy, a 5-point scale test for asthma control was applied. We evaluated the dynamics of total score of asthma controllability 12 weeks after administration of standard therapy in children depending on the allelic variants of rs510432 in gene ATG5 and rs4769628 in gene POMP. Results. Polymorphisms rs510432 in gene ATG5 and rs4769628 in gene POMP have antagonistic interaction. The high risk of atopic diseases is detected in such combinations: heterozygous (CT) or minor (TT) genotype of ATG5 gene in combination with heterozygous (AG) or major (AA) genotypes of gene POMP. During standard therapy for 12 weeks, the average score of total asthma controllability was significantly higher in patients with major and heterozygous variants of rs510432 polymorphism in gene ATG5 than in patients with minor genotype (p < 0.05). In patients with heterozygous genotype AG rs4769628 in gene POMP, the average score of total asthma controllability was significantly higher than in children with major variant of AA genotype (p < 0.05). Conclusions. We have identified combinations of allelic variations rs510432 of gene ATG5 and rs4769628 in gene POMP associated with a high risk of atopic diseases in children. The average score of total asthma controllability depends on polymorphisms rs510432 in gene ATG5 and rs4769628 in gene POMP.

Keywords


single nucleotide polymorphism; autophagy; ATG5; proteasomal proteolysis; РОМР; bronchial asthma; children

References


Banaduga NV, Voloshin SB [The genetic markers that define the origin and course of asthma in children] Sovremennaya pediatriya. 2016, 2(74): 100-104. Ukrainian.

Besh LV, Bondarchuk VO [The study of the effectiveness of the incremental algorithm medical tactics in children with uncontrolled asthma] J Zdorov'e rebenka. 2010, 3(24): 8-13. Ukrainian.

Volosovets OP, Dosenko VE, Krivopustov SP, Pavlyk OV, Iemets OV, Sroy DO [The value of single-nucleotide polymorphism in genes mTOR (rs11121704) and ATG5 (rs510432) in the development of allergic diseases in children] J Zdorov'e rebenka. 2015, 3(63): 5-11. Ukrainian.

Volosovets OP, Dosenko VE, Krivopustov SP, Pavlyk OV, Iemets OV, Sroy DO [Association of gene variations POMP, FLG, MTOR, ATG5 with the risk of asthma in children] J Zdorov'e rebenka. 2016, (1): 18-24. Ukrainian.

Iemets OV [Significance of single-nucleotide polymorphisms rs47696281 in POMP gene in the development of atopic diseases in children] J Zdorov'e rebenka. 2016, 4 (72): 7-12. Ukrainian.

Petrov VI, Shyshymorov IN, Mahnytskaya OV, Tolkachev BE [Personalized medicine: the evolution of the methodology and practical implementation issues] Vestnik VolGMU. 2016, 1(57): URL: http://cyberleninka.ru/article/n/personalizirovannaya-meditsina-evolyutsiya-metodologii-i-problemy-prakticheskogo-vnedreniya. Russian.

Adcock IM, Caramori G [Cross-talk between pro-inflammatory transcription factors and glucocorticoids] Immunol Cell Biol. 2001, 79 (4): 376–84. English.

Cuervo AM [Chaperone-mediated autophagy: selectivity pays] Trends off Endocrinol Metab. 2010, 21(3): 142–150. English.

Ding WX., Yin XM [Sorting, recognition and activation of the misfolded protein degradation pathways through macroautophagy and the proteasome] Autophagy. 2008, 4 (2): 141–50. English.

Gao Z, Gammoh N, Wong PM, Erdjument-Bromage H, Tempst P, Jiang X [Processing of autophagic protein LC3 by the 20S proteasome] Autophagy. 2010, 6 (1): 126–37. English.

Haughney J, Price D, Kaplan A, Chrystyn H, Horne R, May N, Moffat M, Versnel J, Shanahan ER, Hillyer EV, Tunsäter A, Bjermer L [Achieving asthma control in practice: understanding the reasons for poor control] Respir Med. 2008, 102 (12): 1681-93. English.

Lilienbaum A [Relationship between the proteasomal system and autophagy] Int J Biochem Mol Biol. 2013, 4 (1): 1–26. English.

Liu H, Ni S, Zhang Y, Ding L, Zhang Y [Identification of proteasome subunit beta type 3 involved in the potential mechanism of corticosteroid protective effectiveness on beta-2 adrenoceptor desensitization by a proteomics approach] J Thorac Dis. 2013, 5 (6). 797-805. English.

Liu JN, Suh DH, Trinh HK, Chwae YJ, Park HS, Shin YS [The role of autophagy in allergic inflammation: a new target for severe asthma] Exp Mol Med. 2016, 48 (4): e243. doi: 10.1038/emm.2016.38. English.

Liu N, Wang W, Zhao Z, Zhang T, Song Y [Autophagy in human articular chondrocytes is cytoprotective following glucocorticoid stimulation] Mol Med Rep. 2014, 9 (6): 2166-72. English.

Martin LJ, Gupta J, Jyothula SS, Butsch Kovacic M, Biagini Myers JM, Patterson TL, Ericksen MB, He H, Gibson AM, Baye TM, Amirisetty S, Tsoras AM, Sha Y, Eissa NT, Hershey GK [Functional variant in the autophagy-related 5 gene promotor is associated with childhood asthma] PLoS One. 2012, 7 (4): e33454. English.

Meyers DA, Bleecker ER, Holloway JW, Holgate ST [Asthma genetics and personalised medicine] Lancet Respir Med. 2014, 2 (5): 405-15. English.

Moutzouris JP, Che W, Ramsay EE, Manetsch M, Alkhouri H, Bjorkman AM, Schuster F, Ge Q, Ammit AJ [Proteasomal inhibition upregulates the endogenous MAPK deactivator MKP-1 in human airway smooth muscle: mechanism of action and effect on cytokine secretion] Biochim Biophys Acta. 2010, 1803 (3): 416–23. English.

Ortega VE, Meyers DA, Bleecker ER [Asthma pharmacogenetics and the development of genetic profiles for personalized medicine] Pharmgenomics Pers Med. 2015, 16 (8): 9-22. English.

Pelaia G, Cuda G, Vatrella A, Gallelli L, Caraglia M, Marra M, Abbruzzese A, Caputi M, Maselli R, Costanzo FS, Marsico SA [Mitogen-activated protein kinases and asthma] J. Cell Physiol. 2005, 202: 642–653. English.

Savenije OE, Kerkhof M, Koppelman GH, Postma DS [Predicting who will have asthma at school age among preschool children] J Allergy Clin Immunol. 2012, 130 (2): 325-31. English.

Shin Y, Klucken J, Patterson C, Hyman BT, McLean PJ [The co-chaperone carboxyl terminus of Hsp70-interacting protein (CHIP) mediates alpha-synuclein degradation decisions between proteasomal and lysosomal pathways] J Biol Chem. 2005, 280 (25): 23727–34. English.

Wegmann M, Lunding L, Orinska Z, Wong DM, Manz RA, Fehrenbach H [Long-term bortezomib treatment reduces allergen-specific IgE but fails to ameliorate chronic asthma in mice] Int Arch Allergy Immunol. 2012, 158 (1): 43–53. English.




DOI: https://doi.org/10.22141/2224-0551.6.74.2016.82124

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