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Characterization of genetic variation in TLR 8 in relation to allergic rhinitis
Author(s) -
Henmyr V.,
LindHalldén C.,
Carlberg D.,
Halldén C.,
Melén E.,
Wickman M.,
Bergström A.,
Säll T.,
Cardell L. O.
Publication year - 2016
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/all.12805
Subject(s) - immunology , allergy , genetic variation , variation (astronomy) , medicine , biology , genetics , gene , physics , astrophysics
Background A previous investigation of all 10 TLR genes for associations with allergic rhinitis ( AR ) detected a number of significant SNP s in the TLR 8 locus. The associations indicated that an accumulation of rare variants could explain the signal. This study therefore searches for rare variants in the TLR 8 region and also investigates the reproducibility of previous SNP associations. Methods The TLR 8 gene was resequenced in 288 AR patients from Malmö and the data were compared with publically available data. Seven previously AR ‐associated SNP s from TLR 8 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 TLR 8 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 TLR 8 and AR .