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  • Title: Characterization of genetic variation in TLR8 in relation to allergic rhinitis.
    Author: Henmyr V, Lind-Halldén C, Carlberg D, Halldén C, Melén E, Wickman M, Bergström A, Säll T, Cardell LO.
    Journal: Allergy; 2016 Mar; 71(3):333-41. PubMed ID: 26556310.
    Abstract:
    BACKGROUND: A previous investigation of all 10 TLR genes for associations with allergic rhinitis (AR) detected a number of significant SNPs in the TLR8 locus. The associations indicated that an accumulation of rare variants could explain the signal. This study therefore searches for rare variants in the TLR8 region and also investigates the reproducibility of previous SNP associations. METHODS: The TLR8 gene was resequenced in 288 AR patients from Malmö and the data were compared with publically available data. Seven previously AR-associated SNPs from TLR8 were analyzed for AR associations in 422 AR patients and 859 controls from the BAMSE cohort. The associations detected in present and previous studies were compared. RESULTS: Sequencing detected 13 polymorphisms (three promotor and 10 coding) among 288 AR patients. Four of the coding polymorphisms were rare (MAF < 1%) and three of those were novel. Two coding polymorphisms were benign missense mutations and the rest were synonymous. Comparison with 1000Genomes and Exome Aggregation Consortium data revealed no accumulation of rare variants in the AR cases. The AR association tests made using the BAMSE cohort yielded five P-values <0.05. Tests of IgE levels yielded four significant SNP associations to birch pollen. Comparing results between different populations revealed opposing risk alleles, different gender effects, and response to different allergens in the different populations. CONCLUSIONS: Rare variants in TLR8 are not associated with AR. Comparison of present and previous association studies reveals contradictory results for common variants. Thus, no associations exist between genetic variation in TLR8 and AR.
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