1. Genetic variations in the TLR3 locus are associated with eosinophilic esophagitis
- Author
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Alfredo J. Lucendo, Robledo Ávila-Castellano, Stefan Cimbollek, Joaquín Quiralte, Juan-Manuel Bozada, J.R. García-Lozano, [Avila-Castellano, Robledo] Hosp Univ Virgen del Rocio, Div Allergy, UGC Interctr, Seville, Spain, [Cimbollek, Stefan] Hosp Univ Virgen del Rocio, Div Allergy, UGC Interctr, Seville, Spain, [Quiralte, Joaquin] Hosp Univ Virgen del Rocio, Div Allergy, UGC Interctr, Seville, Spain, [Garcia-Lozano, Jose-Raul] Univ Seville, CSIC, Hosp Univ Virgen del Rocio, Serv Inmunol,Unidad Gest Clin Labs Clin,Inst Biom, Seville, Spain, [Lucendo, Alfredo J.] Hosp Gen Tomelloso, Dept Gastroenterol, Tomelloso, Spain, [Lucendo, Alfredo J.] Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid, Spain, [Bozada, Juan-Manuel] Hosp Univ Virgen del Rocio, Div Gastroenterol, Seville, Spain, Alergosur, Sociedad Andaluza de Alergologia e Inmunologia Clinica, Plan Andaluz de Investigacion, and El Fondo Europeo de Desarrollo Regional (FEDER)
- Subjects
0301 basic medicine ,Thymic stromal lymphopoietin ,Cells ,Population ,Locus (genetics) ,Single-nucleotide polymorphism ,03 medical and health sciences ,0302 clinical medicine ,Toll-like receptor ,single nucleotide polymorphism ,Genetic variation ,Food allergy ,Genetic predisposition ,medicine ,Eosinophilic esophagitis ,Children ,business.industry ,Gastroenterology ,Variants ,medicine.disease ,030104 developmental biology ,Oncology ,Immunology ,030211 gastroenterology & hepatology ,business ,Esophagitis ,genetic susceptibility - Abstract
Background Eosinophilic esophagitis (EoE) is an antigen-driven disease mediated by an abnormal immune Th2 response. Objective The objective of this article is to investigate genes associated with regulating immune responses leading to disease susceptibility. Methods Twenty-seven tag single nucleotide polymorphisms (tSNPs) selected in five candidate genes ( TLR3, TLR4, FOXP3, FLG and TSLP) were genotyped in 218 EoE patients and 376 controls. Skin prick tests were carried out in EoE patients with a panel of 17 aeroallergens and 22 plant- and animal-derived foods. Results Five tSNPs located in the TSLP locus and one tSNP located in the TLR3 locus were significantly associated with EoE. The interactions between TLR3 and TSLP loci were analyzed. TLR3+/TSLP– and TLR3–/TSLP+ individuals showed a significantly reduced susceptibility to EoE compared to TLR3–/TSLP– individuals (OR = 0.66, p = 0.036 and OR = 0.23, p = 0.00014, respectively). Likewise, TLR3+/TSLP+ individuals showed the most decreased susceptibility of developing EoE (OR = 0.16, p = 0.0001). However, the interaction gain attributed to the combination of both genes was negative (IG = –4.52%), which indicated redundancy or independent effect. Additionally, TLR3 locus was found to be associated with aeroallergen and food sensitization in EoE patients (OR = 9.67, pc = 0.025 and OR = 0.53, pc = 0.048, respectively). Conclusion TLR3 constitutes a novel genetic susceptibility locus for developing EoE, and the effects would be independent of TSLP.
- Published
- 2018