Genotype-associated prognosis of mono-organ and poly-organ atopic marching phenotypes in children
DOI:
https://doi.org/10.15574/SP.2023.132.16Keywords:
atopic march, children, phenotypes, single nucleotide variants, rs11466749 TSLP, rs7216389 ORMDL3, rs 10052957 h-GR/NR3C1Abstract
Purpose - to research the influence of the single nucleotide variants (SNV) as of thymic stromal lymphopoietin genes (rs11466749 TSLP), orsomucoid-1-like protein 3 (rs7216389 ORMDL3) and human nuclear glucocorticoid receptor type 3 subfamily C member 1 gene (rs 10052957 h-GR/NR3C1) on the risk of developing AM phenotypes «AD», «AD+AR/ARC», «AD+AR/ARC+BA».
Materials and methods. 127 children in the main and 105 in the control group aged from 3 to 18 were recruited into the study. All patients underwent the oral cavity mucosa swab, the material of which was subjected genotyping by the means of real-time polymerase chain reaction for SNV variants rs11466749 TSLP, rs7216389 ORMDL3 and rs 10052957 h-GR/NR3C1. For statistical processing the Pearson’s ꭕ2 criteria, Fisher’s exact test, Student’s test was used; the results were considered significant at p<0.05, trending to significance - at p=0.05-0.1.
Results. The impact of the studied SNV on the risk of the poly-organ phenotype «AD+AR/ARC» development correlated to the mono-organ ««AD»: G/G rs11466749 TSLP: rs=0.173, OR=5.85 (p=0.08); C/T rs7216389 ORMDL3: rs=0.227, OR=0.36 (p<0.05), T/T rs7216389 ORMDL3: rs=0.227, OR=2.79 (p<0.05); A/G rs 10052957 h-GR/NR3C1: rs=0.215, OR=0.40 (p<0.05), G/G rs 10052957 h-GR/NR3C1: rs=0.263, OR=2.97 (p<0.01). The impact of the studied SNV on the development of the full poly-organ AM phenotype «AD+AR/ARC+BA» correlated to the mono-organ «AD»: A/A rs11466749 TSLP: rs=0.207, OR=2.71 (p=0.09), A/G rs11466749 TSLP: rs=0.310, OR=0.17 (p<0.01), G/G rs11466749 TSLP: rs=0.213, OR=7.43 (p=0.09).
Conclusions. Different SNV variants of rs11466749 TSLP, rs7216389 ORMDL3, rs 10052957 h-GR/NR3C1 have both inducing and protective impact on the development of mono-organ and poly-organ AM phenotypes in children. The risk of the mono-organ phenotype «AD» developing into the poly-organ «AD+AR/ARC» is directly associated and significantly increased in carriers of the genotypes T/T rs7216389 ORMDL3 and G/G rs 10052957 h-GR/NR3C1, trending to significance - within G/G rs11466749 TSLP. The bespoke risk is significantly reduced in carriers of C/T rs7216389 ORMDL3 and A/G rs 10052957 h-GR/NR3C1 genotypes. The risk of developing a full poly-organ AM phenotype «AD+AR/ARC+BA» from mono-organ «AD» is significantly reduced in carriers of the A/G rs11466749 TSLP genotype, and is with trend to significance increased within homozygous A/A and G/G rs11466749 TSLP genotypes.
The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patients and children’s parents was obtained for conducting the studies.
No conflict of interests was declared by the author.
References
Bin L, Leung DY. (2016, Oct 19). Genetic and epigenetic studies of atopic dermatitis. Allergy Asthma Clin Immunol. 12: 52. https://doi.org/10.1186/s13223-016-0158-5; PMid:27777593 PMCid:PMC5069938
Chang J, Mitra N, Hoffstad O, Margolis DJ. (2017, Mar 1). Association of Filaggrin Loss of Function and Thymic Stromal Lymphopoietin Variation With Treatment Use in Pediatric Atopic Dermatitis. JAMA Dermatol. 153 (3): 275-281. https://doi.org/10.1001/jamadermatol.2016.4467; PMid:27902816
Das S, Miller M, Broide DH. (2017). Chromosome 17q21 Genes ORMDL3 and GSDMB in Asthma and Immune Diseases. Adv Immunol. 135: 1-52. https://doi.org/10.1016/bs.ai.2017.06.001; PMid:28826527
Dytiatkovsky VO, Abaturov OE, Naumenko NV, Pinayeva NL, Alifirenko OO. (2019). Associations of genotype variants of single nucleotide polymorphism of gene orosomucoid-1-like-protein 3 and atopic diseases at children. Med Perspekt. 24 (3): 67-73. https://doi.org/10.26641/2307-0404.2019.3.181882
Dytiatkovskyi VO. (2021). Role of single nucleotide variants of thymic stromal lymphopoietin in the mono- and poly-organic lesions within atopic disorders in children. Modern Pediatrics. Ukraine. 8 (120): 23-29. https://doi.org/10.15574/SP.2021.120.23
Elmose C, Thomsen SF. (2015). Twin Studies of Atopic Dermatitis: Interpretations and Applications in the Filaggrin Era. J Allergy (Cairo): 902359. https://doi.org/10.1155/2015/902359; PMid:26448767 PMCid:PMC4581550
Han H, Thelen TD, Comeau MR, Ziegler SF. (2014, Dec). Thymic stromal lymphopoietin-mediated epicutaneous inflammation promotes acute diarrhea and anaphylaxis. J Clin Invest. 124 (12): 5442-5452. https://doi.org/10.1172/JCI77798; PMid:25365222 PMCid:PMC4348967
Hill DA, Grundmeier RW, Ram G, Spergel JM. (2016, Aug 20). The epidemiologic characteristics of healthcare provider-diagnosed eczema, asthma, allergic rhinitis, and food allergy in children: a retrospective cohort study. BMC Pediatr. 16: 133. https://doi.org/10.1186/s12887-016-0673-z; PMid:27542726 PMCid:PMC4992234
Hill DA, Spergel JM. (2018, Feb). The atopic march: Critical evidence and clinical relevance. Ann Allergy Asthma Immunol. 120 (2): 131-137. https://doi.org/10.1016/j.anai.2017.10.037; PMid:29413336 PMCid:PMC5806141
Jimenez J, Paller AS. (2021, Sep). The atopic march and its prevention. Ann Allergy Asthma Immunol. 127 (3): 289-290. https://doi.org/10.1016/j.anai.2021.04.021; PMid:33901675
Liang Y, Chang C, Lu Q. (2016, Dec). The Genetics and Epigenetics of Atopic Dermatitis-Filaggrin and Other Polymorphisms. Clin Rev Allergy Immunol. 51 (3): 315-328. https://doi.org/10.1007/s12016-015-8508-5; PMid:26385242
Liu Y, Bochkov YA, Eickhoff JC, Hu T, Zumwalde NA, Tan JW et al. (2020, Jun). Orosomucoid-like 3 Supports Rhinovirus Replication in Human Epithelial Cells. Am J Respir Cell Mol Biol. 62 (6): 783-792. https://doi.org/10.1165/rcmb.2019-0237OC; PMid:32078788 PMCid:PMC7258826
Miyake Y, Hitsumoto S, Tanaka K, Arakawa M. (2015, Aug). Association Between TSLP Polymorphisms and Eczema in Japanese Women: the Kyushu Okinawa Maternal and Child Health Study. Inflammation. 38 (4): 1663-8. https://doi.org/10.1007/s10753-015-0143-z; PMid:25700684
Ono JG, Kim BI, Zhao Y, Christos PJ, Tesfaigzi Y, Worgall TS, Worgall S. (2020). Decreased sphingolipid synthesis in children with 17q21 asthma-risk genotypes. J Clin Invest. 130: 921-926. https://doi.org/10.1172/JCI130860; PMid:31929190 PMCid:PMC6994114
Paller AS, Spergel JM, Mina-Osorio P, Irvine AD. (2019, Jan). The atopic march and atopic multimorbidity: Many trajectories, many pathways. J Allergy Clin Immunol. 143 (1): 46-55. https://doi.org/10.1016/j.jaci.2018.11.006; PMid:30458183
Panek M, Jonakowski M, Zioło J, Wieteska Ł et al. (2016, Jun). 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. 13 (6): 4879-4887. https://doi.org/10.3892/mmr.2016.5104; PMid:27081784
Panek M, Pietras T, Fabijan A, Zioło J et al. (2015, Aug). The NR3C1 Glucocorticoid Receptor Gene Polymorphisms May Modulate the TGF-beta mRNA Expression in Asthma Patients. Inflammation. 38 (4): 1479-1492. https://doi.org/10.1007/s10753-015-0123-3; PMid:25649164
Tsakok T, Marrs T, Mohsin M, Baron S, du Toit G, Till S, Flohr C. (2016, Apr). Does atopic dermatitis cause food allergy? A systematic review. J Allergy Clin Immunol. 137 (4): 1071-1078. https://doi.org/10.1016/j.jaci.2015.10.049; PMid:26897122
Ullemar V, Magnusson PK, Lundholm C, Zettergren A, Melén E, Lichtenstein P, Almqvist C. (2016, Feb). Heritability and confirmation of genetic association studies for childhood asthma in twins. Allergy. 71 (2): 230-238. https://doi.org/10.1111/all.12783; PMid:26786172
Zhang Y, Willis-Owen SAG, Spiegel S, Lloyd CM, Moffatt MF, Cookson WOCM. (2019, Feb 15). The ORMDL3 Asthma Gene Regulates ICAM1 and Has Multiple Effects on Cellular Inflammation. Am J Respir Crit Care Med. 199 (4): 478-488. https://doi.org/10.1164/rccm.201803-0438OC; PMid:30339462 PMCid:PMC6376621
Ziegler SF. (2021, Sep). Thymic stromal lymphopoietin, skin barrier dysfunction, and the atopic march. Ann Allergy Asthma Immunol. 127 (3): 306-311. https://doi.org/10.1016/j.anai.2021.06.004; PMid:34153443 PMCid:PMC8419079
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