Single nucleotide variants of filaggrin and glucocorticoid receptors genes in children suffering different phenotypes of atopic diseases
DOI:
https://doi.org/10.26641/2307-0404.2022.1.254378Keywords:
atopic diseases, children, single nucleotide variants, filaggrin, glucocorticoid receptorsAbstract
Currently, there is an apparent need for genotype-associated personalization of the diagnostic process for atopic diseases (AtD) in children: atopic dermatitis (AD), seasonal allergic rhinitis (conjunctivitis – (SAR(C)), perennial allergic rhinitis (conjunctivitis – (PAR(C)) and bronchial asthma (BA) in different phenotype combinations - monotopic and polytopic. The aim of the study was to identify associations of the genotype variants of SNV rs_7927894 of FLG gene, rs10052957 and rs41423247 of NR3C1 gene in children with AD, SAR(C), PAR(C) and/or BA in mono- and polytopic phenotypes. The study recruited 293 children with AD who were divided into 6 phenotypic clusters: monotopic phenotypes: No. 1 – AD (58 patients); No. 2 – SAR(C)/PAR(C) (71 patients); No. 3 – BA (23 patients); polytopic phenotypes: No. 4 – AD+ SAR(C)/PAR(C) (43 patients), No. 5 – BA+SAR(C)/PAR(C) (72 patients), No. 6-AD+BA+SAR(C)+PAR(C) (26 patients). In patients of all 6 clusters buccal swab of the oral mucosa was taken for genotyping the variants: C/C, C/T, T/T SNV rs7927894 of FLG gene; A/A, A/G, G/G SNV rs10052957 and C/C, C/G, G/G SNV rs41423247 of NR3C1 gene. Heterozygous variant C/T SNV rs_7927894 FLG is the most common, directly associated and significantly increases the risk of polytopic AtD phenotypes: AD+SAR(C)/PAR(C) by 2.47 (95% CI 1.14-5.38, p<0.05) times and AD+BA+SAR(C)+PAR(C) – by 3.13 times (95% CI 1.24-7.95, p<0.05) related to monotopic phenotype SAR(C)/PAR(C). The heterozygous variant A/G SNV rs10052957 of the NR3C1 gene is the most common in all AtD phenotypes, except for monotopic BA and polytopic AD+SAR(C)/PAR(C), and significantly, by 0.40 times (95% CI 0.18-0.93, p<0.05) reduces the risk of the polytopic phenotype related to AD. Homozygous variant G/G SNV rs10052957 of the NR3C1 gene is most common in the monotopic phenotype SAR(C)/PAR(C) and polytopic AD+SAR(C)/PAR(C) as well as in AD+BA+SAR(C)/PAR(C) and significantly increases by 2.97 times (95% CI 1.31-6.74, p<0.05) and decreases by 0.45 times (95% CI 0.21-0.97, p<0.05) the risk of developing AD+SAR(C)/PAR(C) related to AD. Heterozygous variant A/G rs10052957 of the NR3C1 gene significantly reduces by 0.40 times (95% CI 0.18-0.93, p<0.05) the risk of polytopic phenotype BA+SAR(C)+PAR(C) related to AD+SAR(C)/PAR(C). Heterozygous variant C/G SNV 41423247 of the NR3C1 gene was the most common and significantly increased by 2.03 times (95% CI 1.01-4.10, p<0.05) the risk of monotopic AD phenotype related to SAR(C)/PAR(C).
References
Antomonov MY. [Mathematical processing and analysis of medical and biologic data]. Kyiv: IIC «Medinform»; 2018. p. 579. Russian.
Al-Shami HM, Al-Awadi SJ, Khaleel KJ. Association of glucocorticoid receptor gene NR3C1 (Tth111I, Bcli) polymorphisms with asthma children in Iraq. Annals of RSCB. 2021;14055-62.
Dêbiñska A, Danielewicz H, Drabik-Chamerska A, Kalita D, Boznañski A. Chromosome 11q13.5 variant as a risk factor for atopic dermatitis in children. Postepy Dermatol Alergol. 2020;37(1):103-10. doi: https://doi.org/10.5114/ada.2020.93388
Dytiatkovskyi V, Drevytska T, Lapikova-Bryhinska T, Dosenko V, Abaturov O. Genotype associations with the different phenotypes of atopic dermatitis in children. Acta medica (Hradec Kralove). 2021;64(2):96-100. doi: https://doi.org/10.14712/18059694.2021.17
Cheng Z, Dai LL, Liu Q, Liu M, Wang Q, Li PF, et al. Correlation between polymorphisms in the glucocorticoid receptor gene NR3C1 and susceptibility to asthma in a Chinese population from the Henan Province. Genet Mol Res. 2016 Jun 3;15(2). PMID: 27323143. doi: https://doi.org/10.4238/gmr.15028507
Marenholz I, Bauerfeind A, Esparza-Gordillo J, Kerscher T, Granell R, Nickel R, et al. The eczema risk variant on chromosome 11q13 (rs7927894) in the population-based ALSPAC cohort: a novel susceptibility factor for asthma and hay fever. Hum Mol Genet. 2011 Jun 15;20(12):2443-9. doi: https://doi.org/10.1093/hmg/ddr117
Panek M, Jonakowski M, Zioło J, Wieteska Ł, Małachowska B., Pietras T, et al. A novel approach to understanding the role of polymorphic forms of the NR3C1 and TGF-β1 genes in the modulation of the expression of IL-5 and IL-15 mRNA in asthmatic inflammation. Molecular Medicine. Reports 13.6. 2016;4879-87. doi: https://doi.org/10.3892/mmr.2016.5104
Panek M, Pietras T, Fabijan A, Miłanowski M, Wieteska L, Górski P, et al. Effect of glucocorticoid receptor gene polymorphisms on asthma phenotypes. Exp Ther Med. 2013;5:572-80. doi: https://doi.org/10.3892/etm.2012.809
Panek M, Pietras T, Fabijan A, Zioło J, Wieteska Ł, Małachowska B, et al. The NR3C1 glucocorticoid receptor gene polymorphisms may modulate the TGF-beta mRNA expression in asthma patients. Inflammation. 2015 Aug;38(4):1479-92. doi: https://doi.org/10.1007/s10753-015-0123-3
Pietras T, Panek M, Tworek D, Oszajca K, Wujcik R, Górski, et al. The Bcl I single nucleotide polymorphism of the human glucocorticoid receptor gene h-GR/NR3C1 promoter in patients with bronchial asthma: pilot study. Molecular biology reports. 2011;38(6):3953-8. doi: https://doi.org/10.1007/s11033-010-0512-5
Tamari M, Hirota T. Genome-wide association studies of atopic dermatitis. J Dermatol. 2014 Mar;41(3):213-20.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2022 Medicni perspektivi

This work is licensed under a Creative Commons Attribution 4.0 International License.
Submitting manuscript to the journal "Medicni perspektivi" the author(s) agree with transferring copyright from the author(s) to publisher (including photos, figures, tables, etc.) editor, reproducing materials of the manuscript in the journal, Internet, translation into other languages, export and import of the issue with the author’s article, spreading without limitation of their period of validity both on the territory of Ukraine and other countries. This and other mutual duties of the author and all co-authors separately and editorial board are secured by written agreement by special form to use the article, the sample of which is presented on the site.
Author signs a written agreement and sends it to Editorial Board simultaneously with submission of the manuscript.