Evidence map›Paper›PMID 18523153›Full record

Trial reportBlood2008

Regulatory polymorphism in vitamin K epoxide reductase complex subunit 1 (VKORC1) affects gene expression and warfarin dose requirement.

Danxin Wang, Huizi Chen, Kathryn M Momary, Larisa H Cavallari, Julie A Johnson, Wolfgang Sadée

Erratum issuedOpen access · bronzeAbstract readClinical Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Blood, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 92 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
92citing papers in PubMed, 4 pooled it
26.6field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

92 citing papers in PubMed, 4 syntheses or guidelines pooled it, 214 citations in OpenAlex.

  1. Guideline
  2. Pooled it
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32 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

  • Erratum issued
5 · Who and what money

Authors and funding

6 authors at 3 institutions in 1 country.

Danxin WangDepartment of Pharmacology, Program in Pharmacogenetics, College of Medicine, The Ohio State University, Columbus, Ohio 43210, USA. wang.808@osu.edu
Huizi Chen
Kathryn M Momary
Larisa H Cavallari
Julie A Johnson
Wolfgang Sadée
The Ohio State University · USUniversity of Illinois Chicago · USUniversity of Florida · US

Funding

Hypertension PharmacogeneticsR01HL074730 · NHLBI · UNIVERSITY OF FLORIDA · PI JOHNSON, JULIE A. · 2003 to 2006
$3.4M
NHLBI NIH HHS HL 74 730
6 · The paper itself

Abstract

Warfarin dose requirements have been associated with 2 main haplotypes in VKORC1, but the responsible polymorphisms remain unknown. To search for regulatory polymorphisms, we measured allelic mRNA expression of VKORC1 in human liver, heart, and B lymphocytes. The observed 2-fold allelic mRNA expression imbalance narrowed possible candidate SNPs to -1639G>A and 1173C<T. This genotype effect was observed selectively in the liver but not in heart or lymphocytes. In vitro expression of VKORC1 gene constructs, including coding and promoter regions, failed to reveal any genotype effect on transcription and mRNA processing. Chromatin immunoprecipitation with antibodies against acetyl-histone3 and K4-trimethyl-histone3 revealed preferential association of the promoter -1639 G allele with active chromatin, consistent with enhanced mRNA expression. The minor -1639 A allele generates a suppressor E-box binding site, apparently regulating gene expression by a mechanism undetectable with reporter gene assays. A clinical association study demonstrated that promoter SNP -1639G>A, and the tightly linked intron1 SNP 1173C>T, predict warfarin dose more accurately than intron 2 SNP 1542G>C in blacks. Increased warfarin dose requirement in blacks was accounted for by lower frequency of the -1639 A allele. Therefore, -1639G>A is a suitable biomarker for warfarin dosing across ethnic populations.

Indexed as

Polymorphism, Single NucleotideBiopsyBlack PeopleCells, CulturedChromatinEthnicityGene Expression RegulationHumansLiverMixed Function OxygenasesOrgan SpecificityPharmacogeneticsPromoter Regions, GeneticProtein SubunitsRNA, MessengerVitamin K Epoxide ReductasesChromatinMixed Function OxygenasesProtein SubunitsRNA, MessengerVitamin K Epoxide ReductasesVKORC1 protein, humanWarfarin

Identifiers

PMID18523153
PMCPMC2515137
OpenAlexW2085067513

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.