Evidence map›Paper›PMID 20499136›Full record

ArticleJournal of thrombosis and thrombolysis2010

An evaluation of nine genetic variants related to metabolism and mechanism of action of warfarin as applied to stable dose prediction.

John F Carlquist, Benjamin D Horne, Chrissa Mower, James Park, John Huntinghouse, Jason T McKinney, Joseph B Muhlestein, Jeffrey L Anderson

Abstract read
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In one paragraph

Article in Journal of thrombosis and thrombolysis, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed, 3 pooled it
–field-weighted citation impact
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

18 citing papers in PubMed, 3 syntheses or guidelines pooled it.

  1. Pooled it
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  13. The pharmacogenetics of the response to warfarin in Chinese.British journal of clinical pharmacology · 2012
    Review
  14. Article
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  16. Genetic warfarin dosing: tables versus algorithms.Journal of the American College of Cardiology · 2011
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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

8 authors.

John F CarlquistCardiovascular Department, Intermountain Medical Center, 5121 South Cottonwood Street, Murray, UT 84157, USA. john.carlquist@imail.org
Benjamin D Horne
Chrissa Mower
James Park
John Huntinghouse
Jason T McKinney
Joseph B Muhlestein
Jeffrey L Anderson

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Warfarin anticoagulation is complicated by the highly variable inter-individual response. Approximately 50% of the dose variability arises from clinical factors and variants in two genes, CYP2C9 (*2 and *3 variants) and VKORC1 -1173 C > T. We tested variants in five additional genes (EPHX1, PROC, APOE, CYP4F2, CALU and a new variant in VKORC1 in an attempt to further reduce the variability in predicted stable warfarin dose. Consecutive consenting outpatients requiring anticoagulation on stable warfarin dose (target INR 2-3) were genotyped; the association of SNP genotypes with stable warfarin dose was evaluated using the test of linear contrasts in analysis of variance (ANOVA). Study participants were 71 ± 13 years, 53% female, 85 ± 23 kg, body mass index 29 ± 7 kg/m(2). Genotypes were in Hardy-Weinberg equilibrium with the exception of VKORC1 -1639. Weekly stable dosages were 31.7 ± 13.9 mg/week; median: 30 mg/week, range: 11-70 mg/week. Significant associations with dose were seen for VKORC1 -1639 (P < 0.001), CYP2C9*2 (P = 0.005) and *3 (P = 0.003), the CYP4F2 SNP (P-trend = 0.00037), and VKORC1 3730 (p-trend = 0.042). In linear regression, age, sex, weight, and CYP2C9 *2 and *3 and VKORC1-1639 genotype explained 42% of variance. The addition of CYP4F2 genotype to the regression model increased the degree of variance explained to 47%. Addition of VKORC1 SNP -1639 to a model eliminated the association of VKORC1 3730 with warfarin dose (P-trend = 0.74), but -1639 remained highly significant. No impact on dose was observed for the other tested genetic variants.

Indexed as

Polymorphism, Single NucleotideAnimalsApolipoproteins EAryl Hydrocarbon HydroxylasesCalcium-Binding ProteinsCytochrome P-450 CYP2C9Cytochrome P-450 Enzyme SystemCytochrome P450 Family 4Drug ResistanceEpoxide HydrolasesFemaleGenetic Association StudiesHumansMaleMiceMixed Function OxygenasesApolipoproteins EAryl Hydrocarbon HydroxylasesCalcium-Binding ProteinsCALU protein, humanCYP2C9 protein, humanCYP4F2 protein, humanCytochrome P-450 CYP2C9Cytochrome P-450 Enzyme SystemCytochrome P450 Family 4EPHX1 protein, humanEpoxide HydrolasesMixed Function OxygenasesProtein CVitamin K Epoxide ReductasesVKORC1 protein, human

Identifiers

PMID20499136

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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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.