Novel regulatory variant detected on the VKORC1 haplotype that is associated with warfarin dose

Cavalli, Marco (author): Uppsala universitet,Medicinsk genetik och genomik,Science for Life Laboratory, SciLifeLab

Pan, Gang (author): Uppsala universitet,Medicinsk genetik och genomik,Science for Life Laboratory, SciLifeLab

Nord, Helena (author): Uppsala universitet,Medicinsk genetik och genomik,Science for Life Laboratory, SciLifeLab

Eriksson, Niclas (author): Uppsala universitet,Uppsala kliniska forskningscentrum (UCR),Institutionen för medicinska vetenskaper

Wadelius, Claes (author): Uppsala universitet,Medicinsk genetik och genomik,Science for Life Laboratory, SciLifeLab

Wadelius, Mia (author): Uppsala universitet,Klinisk farmakogenomik och osteoporos,Science for Life Laboratory, SciLifeLab

(creator_code:org_t)

Future Medicine Ltd, 2016
2016
English.
In: Pharmacogenomics (London). - : Future Medicine Ltd. - 1462-2416 .- 1744-8042. ; 17:12, s. 1305-1314

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Abstract Subject headings

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.

By the author/editor: Cavalli, Marco; Pan, Gang; Nord, Helena; Eriksson, Niclas; Wadelius, Claes; Wadelius, Mia

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