Analysis of IL-13 gene polymorphisms in pediatric patients with food allergy
Main Article Content
Keywords
IgE-mediated food allergies, IL-13 gene, non-IgE-mediated food allergies, rs1800925, single-nucleotide polymorphisms
Abstract
Food allergies represent immune-mediated adverse reactions to dietary proteins, with incompletely elucidated causes and etiopathogenic mechanisms, and have a significant negative impact on the quality of life of children and their families. The aim of the study was to assess the associations between IL-13 gene single-nucleotide polymorphisms (SNPs) rs20541 and rs1800925 and the risk of developing IgE-mediated or non-IgE-mediated food allergies, as well as other patient characteristics. The study included 115 healthy controls and 165 children with food allergy, divided into two groups based on the presence of either IgE-mediated (N=85) or non-IgE-mediated (N=80) food allergy, all of Romanian origin. Genotyping of the two SNPs was performed using Real-Time PCR with TaqMan Allelic Discrimination Assays. OpenEpi and PLINK v1.07 were used for the statistical analysis. The frequency of carriers of the minor allele T of rs1800925 was significantly higher in patients with non-IgE-mediated food allergy (50% vs. 35.6%, p=0.04, OR=1.8). CT heterozygotes of rs1800925 were at high risk for non-IgE-mediated food allergy compared to CC and TT homozygotes (p=0.01, OR=2.13). No associations were found with IgE-mediated food allergy. The present study investigates for the first time IL-13 gene SNPs in non-IgE-mediated food allergy. The results provide evidence that variation in the IL-13 gene is involved in the pathogenesis of this disease. Further investigation is required to confirm these findings.
References
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3. Venter C, Brown T, Shah N, Walsh J, Fox AT. Diagnosis and management of non-IgE-mediated cow’s milk allergy in infancy - a UK primary care practical guide. Clin Transl Allergy. 2013;3(1):23. 10.1186/2045-7022-3-23
4. Nowak-Węgrzyn A, Katz Y, Mehr SS, Koletzko S. Non–IgE-mediated gastrointestinal food allergy. J Allergy Clin Immunol. 2015;135(5):1114–1124. 10.1016/j.jaci.2015.03.025
5. O’Shea KM, Aceves SS, Dellon ES, Gupta SK, Spergel JM, Furuta GT, Rothenberg ME. Pathophysiology of Eosinophilic Esophagitis. Gastroenterology. 2018;154(2):333–345. 10.1053/j.gastro.2017.06.065
6. Muir A, Falk GW. Eosinophilic Esophagitis: A Review. JAMA. 2021;326(13):1310–1318. 10.1001/jama.2021.14920
7. Dellon ES, Muir AB, Katzka DA, Shah SC, Sauer BG, Aceves SS, Furuta GT, Gonsalves N, Hirano I. ACG Clinical Guideline: Diagnosis and Management of Eosinophilic Esophagitis. Am J Gastroenterol. 2025;120(1):31–59. 10.14309/ajg.0000000000003194
8. Spolidoro GCI, Amera YT, Ali MM, Nyassi S, Lisik D, Ioannidou A, et al. Frequency of food allergy in Europe: An updated systematic review and meta-analysis. Allergy. 2023;78(2):351–368. 10.1111/all.15560
9. Bartha I, Almulhem N, Santos AF. Feast for thought: A comprehensive review of food allergy 2021-2023. J Allergy Clin Immunol. 2024;153(3):576–594. 10.1016/j.jaci.2023.11.918
10. Zhang S, Sicherer S, Berin MC, Agyemang A. Pathophysiology of Non-IgE-Mediated Food Allergy. ImmunoTargets Ther. 2021;10:431–446. 10.2147/ITT.S284821
11. Morita H, Nomura I, Orihara K, Yoshida K, Akasawa A, Tachimoto H, et al. Antigen-specific T-cell responses in patients with non–IgE-mediated gastrointestinal food allergy are predominantly skewed to TH2. J Allergy Clin Immunol. 2013;131(2):590–592.e6. 10.1016/j.jaci.2012.10.052
12. Patel RV, Hirano I, Gonsalves N. Eosinophilic Esophagitis: Etiology and Therapy. Annu Rev Med. 2021;72(1):183–197. 10.1146/annurev-med-042020-112441
13. Rael EL, Lockey RF. Interleukin-13 Signaling and Its Role in Asthma. World Allergy Organ J. 2011;4(3):54–64. 10.1097/WOX.0b013e3182118c68
14. Davis BP. Pathophysiology of Eosinophilic Esophagitis. Clin Rev Allergy Immunol. 2018;55(1):19–42. 10.1007/s12016-017-8665-9
15. Rothenberg ME. Molecular, Genetic, and Cellular Bases for Treating Eosinophilic Esophagitis. Gastroenterology. 2015;148(6):1143–1157. 10.1053/j.gastro.2015.02.002
16. Brandt EE. Th2 Cytokines and Atopic Dermatitis. J Clin Cell Immunol. 2011;02(03). Available from: https://www.omicsonline.org/th2-cytokines-and-atopic-dermatitis-2155-9899.1000110.php?aid=1712
17. Pontikas A, Antonatos C, Evangelou E, Vasilopoulos Y. Candidate Gene Association Studies in Atopic Dermatitis in Participants of European and Asian Ancestry: A Systematic Review and Meta-Analysis. Genes. 2023;14(7):1456. 10.3390/genes14071456
18. Hirano I, Collins MH, Assouline-Dayan Y, Evans L, Gupta S, Schoepfer AM, et al. RPC4046, a Monoclonal Antibody Against IL13, Reduces Histologic and Endoscopic Activity in Patients With Eosinophilic Esophagitis. Gastroenterology. 2019;156(3):592–603.e10. 10.1053/j.gastro.2018.10.051
19. Wang M, Gao XH, Zhang L. A Review of Dupilumab in the Treatment of Atopic Dermatitis in Infants and Children. Drug Des Devel Ther. 2024;18:941–951. 10.2147/DDDT.S457761
20. Marenholz I, Grosche S, Rüschendorf F, Kalb B, Blumchen K, Schlags R, et al. Evaluation of food allergy candidate loci in the Genetics of Food Allergy study. J Allergy Clin Immunol. 2018;142(4):1368–1370.e2. 10.1016/j.jaci.2018.07.012
21. Trzeciak M, Gleń J, Rębała K, Bandurski T, Sikorska M, Nowicki R. Coexistence of 2282del4 FLG gene mutation and IL-18-137G/C gene polymorphism enhances the risk of atopic dermatitis. Adv Dermatol Allergol. 2016;33(1):57–62. 10.5114/pdia.2015.48050
22. Ashley SE, Tan HTT, Peters R, Allen KJ, Vuillermin P, Dharmage SC, Tang MLK, Koplin J, Lowe A, Ponsonby AL, Molloy J, Matheson MC, Saffery R, Ellis JA, Martino D; HealthNuts team. Genetic variation at the Th2 immune gene IL13 is associated with IgE-mediated paediatric food allergy. Clin Exp Allergy. 2017;47(8):1032–1037. 10.1111/cea.12942
23. Laha A, Ghosh A, Moitra S, Biswas H, Saha NC, Bhattacharya S, et al. Association of HLA-DQ and IL13 gene variants with challenge-proven shrimp allergy in West Bengal, India. Immunogenetics. 2020;72(9–10):489–498. 10.1007/s00251-020-01182-5
24. Bottema RWB, Reijmerink NE, Kerkhof M, Koppelman GH, Stelma FF, Gerritsen J, et al. Interleukin 13, CD14, pet and tobacco smoke influence atopy in three Dutch cohorts: the allergenic study. Eur Respir J. 2008;32(3):593–602. 10.1183/09031936.00086707
25. Zitnik SE, Rüschendorf F, Müller S, Sengler C, Lee Y, Griffioen RW, et al. IL13 variants are associated with total serum IgE and early sensitization to food allergens in children with atopic dermatitis. Pediatr Allergy Immunol. 2009;20(6):551–555. 10.1111/j.1399-3038.2009.00832.x
26. Liu X, Beaty TH, Deindl P, Huang SK, Lau S, Sommerfeld C, et al. Associations between specific serum IgE response and 6 variants within the genes IL4, IL13, and IL4RA in German children: The German Multicenter Atopy Study. J Allergy Clin Immunol. 2004;113(3):489–495. 10.1016/j.jaci.2003.12.460
27. Howard TD, Whittaker PA, Zaiman AL, Koppelman GH, Xu J, Hanley MT, et al. Identification and Association of Polymorphisms in the Interleukin-13 Gene with Asthma and Atopy in a Dutch Population. Am J Respir Cell Mol Biol. 2001;25(3):377–384. 10.1165/ajrcmb.25.3.4289
28. Van Der Pouw Kraan T, Van Veen A, Boeije L, Van Tuyl S, De Groot E, Stapel S, et al. An IL-13 promoter polymorphism associated with increased risk of allergic asthma. Genes Immun. 1999;1(1):61–65. 10.1038/sj.gene.6362858
29. Omraninava M, Eslami MM, Aslani S, Razi B, Imani D, Feyzinia S. Interleukin 13 gene polymorphism and susceptibility to asthma: a meta-regression and meta-analysis. Eur Ann Allergy Clin Immunol. 2022;54(4):150–167. 10.23822/EurAnnACI.1764-1489.180
30. Cui L, Jia J, Ma CF, Li SY, Wang YP, Guo XM, et al. IL-13 polymorphisms contribute to the risk of asthma: a meta-analysis. Clin Biochem. 2012;45(4–5):285–288. 10.1016/j.clinbiochem.2011.10.029
31. Heinzmann A. Genetic variants of IL-13 signalling and human asthma and atopy. Hum Mol Genet. 2000;9(4):549–559. 10.1093/hmg/9.4.549.
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