uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • 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
Novel regulatory variant detected on the VKORC1 haplotype that is associated with warfarin dose
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
Show others and affiliations
2016 (English)In: Pharmacogenomics (London), ISSN 1462-2416, E-ISSN 1744-8042, Vol. 17, no 12, 1305-1314 p.Article in journal (Refereed) Published
Abstract [en]

Aim: Warfarin dose requirement is associated with VKORC1 rs9923231, and we studied whether it is a functional variant.

Materials & methods: We selected variants in linkage disequilibrium with rs9923231 that bind transcription factors in an allele-specific way. Representative haplotypes were cloned or constructed, nuclear protein binding and transcriptional activity were evaluated.

Results: rs56314408C>T and rs2032915C>T were detected in a liver enhancer in linkage disequilibrium with rs9923231. The rs56314408-rs2032915 C-C haplotype preferentially bound nuclear proteins and had higher transcriptional activity than T-T and the African-specific T-C. A motif for TFAP2A/C was disrupted by rs56314408T. No difference in transcriptional activity was detected for rs9923231G>A.

Conclusion: Our results supported an activating role for rs56314408C, while rs9923231G>A had no evidence of being functional.

Place, publisher, year, edition, pages
2016. Vol. 17, no 12, 1305-1314 p.
Keyword [en]
regulatory sequences, vitamin K epoxide reductases, warfarin
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-303112DOI: 10.2217/pgs-2015-0013ISI: 000380813600003PubMedID: 26847243OAI: oai:DiVA.org:uu-303112DiVA: diva2:1032975
Available from: 2016-10-05 Created: 2016-09-15 Last updated: 2017-11-30Bibliographically approved

Open Access in DiVA

fulltext(2912 kB)132 downloads
File information
File name FULLTEXT01.pdfFile size 2912 kBChecksum SHA-512
1eada8f3cc0f57d3c87520b94acbdf5f2514040532d3a19ba8ecc892d347ff5e7a4bb991f54f9de5fa39a57cc194776d5af5bcf678f394f83ff8f8ed1e0ccac7
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Cavalli, MarcoPan, GangEriksson, NiclasWadelius, ClaesWadelius, Mia
By organisation
Medicinsk genetik och genomikScience for Life Laboratory, SciLifeLabUCR-Uppsala Clinical Research CenterDepartment of Medical SciencesClinical pharmacogenomics and osteoporosis
In the same journal
Pharmacogenomics (London)
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
Total: 132 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: 589 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • 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