Genetic variations in the TLR3 locus are associated with eosinophilic esophagitis.

ABSTRACT: Eosinophilic esophagitis (EoE) is an antigen-driven disease mediated by an abnormal immune Th2 response.The objective of this article is to investigate genes associated with regulating immune responses leading to disease susceptibility.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.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).TLR3 constitutes a novel genetic susceptibility locus for developing EoE, and the effects would be independent of TSLP.

SUBMITTER: Avila-Castellano R 

PROVIDER: S-EPMC5949969 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature