Evidence map›Paper›PMID 15883587›Full record

ArticleThe pharmacogenomics journal2005

Common VKORC1 and GGCX polymorphisms associated with warfarin dose.

M Wadelius, L Y Chen, K Downes, J Ghori, S Hunt, N Eriksson, O Wallerman, H Melhus, C Wadelius, D Bentley and 1 more

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In one paragraph

Article in The pharmacogenomics journal, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01520402 (Quantitative Pharmacogenomics of the Anticoagulant Response to Warfarin in Healthy Subjects), which is not on this map. Cited by 177 papers, 10 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
177citing papers in PubMed, 10 pooled it
37.6field-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.

NCT01520402 nacompletednot on this mapstarted 2009, after this paper: background citation

Quantitative Pharmacogenomics of the Anticoagulant Response to Warfarin in Healthy Subjects

TypeinterventionalSponsorIcahn School of Medicine at Mount SinaiRan2009 to 2011Enrolled35ConditionsHealthyArmsWarfarin
3 · Its place in the literature

Who cites it

177 citing papers in PubMed, 10 syntheses or guidelines pooled it, 466 citations in OpenAlex.

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  11. Genetic Polymorphism ofClinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis · 2018
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117 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 3 institutions in 2 countries.

M WadeliusDepartment of Medical Sciences, Clinical Pharmacology, University Hospital, Uppsala, Sweden. mia.wadelius@medsci.uu.se
L Y Chen
K Downes
J Ghori
S Hunt
N Eriksson
O Wallerman
H Melhus
C Wadelius
D Bentley
P Deloukas
Wellcome Sanger Institute · GBUppsala University Hospital · SEUppsala University · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

We report a novel combination of factors that explains almost 60% of variable response to warfarin. Warfarin is a widely used anticoagulant, which acts through interference with vitamin K epoxide reductase that is encoded by VKORC1. In the next step of the vitamin K cycle, gamma-glutamyl carboxylase encoded by GGCX uses reduced vitamin K to activate clotting factors. We genotyped 201 warfarin-treated patients for common polymorphisms in VKORC1 and GGCX. All the five VKORC1 single-nucleotide polymorphisms covary significantly with warfarin dose, and explain 29-30% of variance in dose. Thus, VKORC1 has a larger impact than cytochrome P450 2C9, which explains 12% of variance in dose. In addition, one GGCX SNP showed a small but significant effect on warfarin dose. Incorrect dosage, especially during the initial phase of treatment, carries a high risk of either severe bleeding or failure to prevent thromboembolism. Genotype-based dose predictions may in future enable personalised drug treatment from the start of warfarin therapy.

Indexed as

Polymorphism, Single NucleotideAdultAgedAged, 80 and overAnticoagulantsCarbon-Carbon LigasesDose-Response Relationship, DrugFemaleHaplotypesHumansMaleMiddle AgedMixed Function OxygenasesRegression AnalysisVitamin K Epoxide ReductasesWarfarinAnticoagulantsCarbon-Carbon Ligasesglutamyl carboxylaseMixed Function OxygenasesVitamin K Epoxide ReductasesVKORC1 protein, humanWarfarin

Identifiers

PMID15883587
OpenAlexW2038118250

What OpenQuestion holds

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Read underepoch 390

Registered trials

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.