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Genetic variations in the TLR3 locus are associated with eosinophilic esophagitis
- Publication Year :
- 2018
- Publisher :
- Sage publications inc, 2018.
-
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.
- 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
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....fc5eec8e79ed585b68371a38649e3779