Personalized genotype markers of the atopic disorders phenotypes in children
Keywords:atopic disorders, children, mono-organic phenotypes, poly-organic phenotypes, single nucleotide variants
The goal of the study was to elucidate the impact of the single nucleotide variants rs11466749 of the thymic stromal lymphopoietin gene, rs_7216389 of the orsomucoid-1-like protein 3 gene, and rs10052957 of the human nuclear glucocorticoid receptor subfamily 3, group C, member 1 gene on the development of the mono-organic phenotype “atopic eczema” or the poly-organic “atopic eczema + allergic rhinitis/allergic rhino-conjunctivitis”. We recruited 101 patients into the main and 105 into control groups aged from 3 to 18 years old. Patients of the main group suffered from atopic eczema (58 children) and atopic eczema + allergic rhinitis/allergic rhino-conjunctivitis (43 children). Patients of the control group suffered from the digestive tract pathology. Main group patients were genotyped for the A/A, A/G, G/G of rs11466749, C/T, C/C and T/T of rs_7216389 and A/A, A/G and G/G of rs10052957; patients of the control group were genotyped for the A/A, A/G, G/G of rs11466749, C/T, C/C and T/T of rs_7216389 by polymerase chain reaction in real time with restricted fragment length polymorphism. Results: no significant differences in rs11466749 among the main and control groups, the most common variant is A/A – 55.2% (mono-organic) and 55.8% (poly-organic); T/T rs_7216389 is significantly the most common in poly-organic phenotype – 39.5%; rs10052957: A/G variant is significantly most common in mono-organic phenotype – 51.7% and G/G – in the poly-organic phenotype – 62.8%. The G/G rs11466749 variant has a trending to significance direct 0.173 association and increased odds ratio = 5.85 (0.63-54.31) for the poly-organic phenotype and protective impact onto the mono-organic phenotype -0.173 (0.17 (0.02-1.59); T/T rs7216389 variant increases the risk of poly-organic phenotype: 0.227, odds ratio = 2,79 (1.14-6.85) and decreases the risk of mono-organic” phenotype: -0.227, 0.36 (0.15-0.88); A/G rs_10052957 variant significantly increases the risk the mono-organic phenotype: 0.215, odds ratio = 2.5 (1.08-5.56)) and decreases risk of poly-organic phenotype: 0.215, odds ratio = 0.4 (0.18-0.93); G/G rs_10052957 variant significantly increases the risk of the poly-organic phenotype: 0.263, odds ratio = 2.97 (1.31-6.74)) and decreases for the mono-organic phenotype: -0.263, odds ratio = 0.34 (0.15-0.76)). Genotype variant T/T rs_7216389 of the orsomucoid-1-like protein 3 gene significantly increases the risk of developing the poly-organic atopic phenotype by 2.79 times and protects against the mono-organic atopic phenotype by 0.34 times. G/G genotype variant of rs10052957 of the human glucocorticoid receptor subfamily, group C, member 1 gene significantly increases the risk of developing the poly-organic phenotype by 2.97 times, protecting against mono-organic atopic phenotype by 0.34 times.
Keller W, Vogel M, Prenzel F, Genuneit J, Jurkutat A, Hilbert C, et al. Atopic diseases in children and adolescents are associated with behavioural difficulties. BMC Pediatr. 2021;21(1):197. doi: http://dx.doi.org/10.1186/s12887-021-02663-7
Hill DA, Spergel JM. The atopic march. Ann Allergy Asthma Immunol. 2018;120(2):131-7. doi: http://dx.doi.org/10.1016/j.anai.2017.10.037
Torres T, Ferreira EO, Gonçalo M, Mendes-Bastos P, Selores M, Filipe P. Update on Atopic Dermatitis. Acta Med Port. 2019;32(9):606-13. doi: http://dx.doi.org/10.20344/amp.11963
Løset M, Brown SJ, Saunes M, Hveem K. Genetics of atopic dermatitis: From DNA sequence to clinical relevance. Dermatology. 2019;235(5):355-64. doi: http://dx.doi.org/10.1159/000500402
Sroka-Tomaszewska J, Trzeciak M. Molecular mechanisms of atopic dermatitis pathogenesis. Int J Mol Sci. 2021;22(8):4130. doi: http://dx.doi.org/10.3390/ijms22084130
Čepelak I, Dodig S, Pavić I. Filaggrin and atopic march. Biochem Med (Zagreb). 2019;29(2):214-27. doi: http://dx.doi.org/10.11613/bm.2019.020501
Dytiatkovsky VO, Abaturov OE, Naumenko NV, Pinayeva NL, Alifirenko OO. Associations of genotype variants of single nucleotide polymorphism of gene orosomucoid-1-like-protein 3 and atopic diseases at children. Medicni perspektivi. 2019;24(3):67-73. doi: http://dx.doi.org/10.26641/2307-0404.2019.3.181882
Al-Shami HM, Al-Awadi SJ, Khaleel KhJ. Asso-ciation of Glucocorticoid Receptor Gene NR3C1 (Tth111I, Bcli) Polymorphisms with Asthma Children in Iraq. Annals of RSCB. 2021 May 4:1405562. Available from: https://www.annalsofrscb.ro/index.php/journal/article/view/4553
Birben E, Sahiner UM, Karaaslan C, Yavuz TS, Cosgun E, Kalayci O, et al. The genetic variants of thymic stromal lymphopoietin protein in children with asthma and allergic rhinitis. Int Arch Allergy Immunol. 2014;163(3):185-92. doi: http://dx.doi.org/10.1159/000358488
Heo WI, Park KY, Lee M-K, Moon NJ, Seo SJ. TSLP polymorphisms in atopic dermatitis and atopic march in Koreans. Ann Dermatol. 2018;30(5):529. doi: http://dx.doi.org/10.5021/ad.2018.30.5.529
Dytiatkovskyi VO. Role of single nucleotide variants of thymic stromal lymphopoietin in the mono- and polyorganic lesions within atopic disorders in children. Modern pediatrics Ukraine. 2021;8(120):23-9. doi: http://dx.doi.org/10.15574/sp.2021.120.23
Antomonov MY. [Mathematical processing and analysis of medical and biologic data]. Kyiv: IIC «Med-inform»; 2018. 579 p. Russian.
Lou C, Mitra N, Wubbenhorst B, D’Andrea K, Hoffstad O, Kim BS, et al. Association between fine mapping thymic stromal lymphopoietin and atopic dermatitis onset and persistence. Ann Allergy Asthma Immunol. 2019;123(6):595-601.e1. doi: http://dx.doi.org/10.1016/j.anai.2019.08.018
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: http://dx.doi.org/10.14712/18059694.2021.17
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. Mol Med Rep. 2016;13(6):4879-87. doi: http://dx.doi.org/10.3892/mmr.2016.5104
How to Cite
Copyright (c) 2023 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.