Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Genetic variation of the toll-like receptors in a Swedish allergic rhinitis case population
Kristianstad University, School of Education and Environment, Avdelningen för Naturvetenskap. Kristianstad University, Forskningsmiljön Biomedicin. Lund University.
Kristianstad University, School of Education and Environment, Avdelningen för Naturvetenskap. Kristianstad University, Forskningsmiljön Biomedicin.
Kristianstad University, School of Education and Environment, Avdelningen för Naturvetenskap. Kristianstad University, Plattformen för molekylär analys. Lund University.
Kristianstad University, School of Education and Environment, Avdelningen för Naturvetenskap. Kristianstad University, Forskningsmiljön Biomedicin.
Show others and affiliations
2017 (English)In: BMC Medical Genetics, ISSN 1471-2350, E-ISSN 1471-2350, Vol. 18, no 1, article id 18Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Variation in the 10 toll-like receptor (TLR) genes has been significantly associated with allergic rhinitis (AR) in several candidate gene studies and three large genome-wide association studies. These have all investigated common variants, but no investigations for rare variants (MAF ≤ 1%) have been made in AR. The present study aims to describe the genetic variation of the promoter and coding sequences of the 10 TLR genes in 288 AR patients.

METHODS: Sanger sequencing and Ion Torrent next-generation sequencing was used to identify polymorphisms in a Swedish AR population and these were subsequently compared and evaluated using 1000Genomes and Exome Aggregation Consortium (ExAC) data.

RESULTS: The overall level of genetic variation was clearly different among the 10 TLR genes. The TLR10-TLR1-TLR6 locus was the most variable, while the TLR7-TLR8 locus was consistently showing a much lower level of variation. The AR patients had a total of 37 promoter polymorphisms with 14 rare (MAF ≤ 1%) and 14 AR-specific polymorphisms. These numbers were highly similar when comparing the AR and the European part of the 1000Genomes populations, with the exception of TLR10 where a significant (P = 0.00009) accumulation of polymorphisms were identified. The coding sequences had a total of 119 polymorphisms, 68 were rare and 43 were not present in the European part of the 1000Genomes population. Comparing the numbers of rare and AR-specific SNPs in the patients with the European part of the 1000Genomes population it was seen that the numbers were quite similar both for individual genes and for the sum of all 10 genes. However, TLR1, TLR5, TLR7 and TLR9 showed a significant excess of rare variants in the AR population when compared to the non-Finnish European part of ExAC. In particular the TLR1 S324* nonsense mutation was clearly overrepresented in the AR population.

CONCLUSIONS: Most TLR genes showed a similar level of variation between AR patients and public databases, but a significant excess of rare variants in AR patients were detected in TLR1, TLR5, TLR7, TLR9 and TLR10. This further emphasizes the frequently reproduced TLR10-TLR1-TLR6 locus as being involved in the pathogenesis of allergic rhinitis.

Place, publisher, year, edition, pages
2017. Vol. 18, no 1, article id 18
Keywords [en]
Allergic rhinitis, Mutation spectrum, Next-generation sequencing, Rare variants, Toll-like receptor
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:hkr:diva-16592DOI: 10.1186/s12881-017-0379-6ISI: 000397484800001PubMedID: 28228119OAI: oai:DiVA.org:hkr-16592DiVA, id: diva2:1082319
Funder
Swedish Research CouncilAvailable from: 2017-03-16 Created: 2017-03-16 Last updated: 2017-11-29Bibliographically approved

Open Access in DiVA

fulltext(919 kB)43 downloads
File information
File name FULLTEXT01.pdfFile size 919 kBChecksum SHA-512
26b0abcdd2a23dbebd74273bae6fea840e80c6bf7e421f205561b950945861da4c38b744261868f0aee43c70f289d2d6623542528f97639bf50e378065bad40e
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Henmyr, ViktorCarlberg, DanielManderstedt, EricLind-Halldén, ChristinaHalldén, Christer
By organisation
Avdelningen för NaturvetenskapForskningsmiljön BiomedicinPlattformen för molekylär analys
In the same journal
BMC Medical Genetics
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
Total: 43 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 97 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf