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Characterization of genetic variation in TLR8 in relation to allergic rhinitis
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2015 (English)In: Allergy. European Journal of Allergy and Clinical Immunology, ISSN 0105-4538, E-ISSN 1398-9995Article in journal (Refereed) Published
Abstract [en]

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. The present study therefore searches for rare variants in the TLR8 region and also investigates the reproducibility of previous SNP associations.

METHODS: The TLR8 gene was re-sequenced in 288 AR patients from Malmö and the data was 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 (3 promotor, 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 5 P-values < 0.05. Tests of IgE-levels yielded 4 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 reveal contradictory results for common variants. Thus, no associations exist between genetic variation in TLR8 and AR. This article is protected by copyright. All rights reserved.

Place, publisher, year, edition, pages
2015.
Keyword [en]
Adolescents, depression, school-based program, prevention, cognitive behavior program
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Medical and Health Sciences
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URN: urn:nbn:se:hkr:diva-15026DOI: 10.1111/all.12805PubMedID: 26556310OAI: oai:DiVA.org:hkr-15026DiVA: diva2:872297
Available from: 2015-11-18 Created: 2015-11-18 Last updated: 2015-11-18Bibliographically approved

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Henmyr, ViktorLind-Halldén, ChristinaCarlberg, DanielHalldén, Christer

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