RT Journal Article
T1 Genetic variations in the TLR3 locus are associated with eosinophilic esophagitis
A1 Avila-Castellano, Robledo
A1 Garcia-Lozano, Jose-Raul
A1 Cimbollek, Stefan
A1 Lucendo, Alfredo J.
A1 Bozada, Juan-Manuel
A1 Quiralte, Joaquin
K1 Eosinophilic esophagitis
K1 genetic susceptibility
K1 thymic stromal lymphopoietin
K1 Toll-like receptor
K1 single nucleotide polymorphism
K1 Thymic stromal lymphopoietin
K1 Food allergy
K1 Variants
K1 Population
K1 Children
K1 Cells
AB 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, p(c) = 0.025 and OR = 0.53, p(c) = 0.048, respectively).Conclusion: TLR3 constitutes a novel genetic susceptibility locus for developing EoE, and the effects would be independent of TSLP.
PB Sage publications inc
SN 2050-6406
YR 2018
FD 2018-04-01
LK http://hdl.handle.net/10668/19107
UL http://hdl.handle.net/10668/19107
LA en
DS RISalud
RD Apr 18, 2025