Evidence map›Paper›PMID 21562147›Full record

ArticleDrug metabolism and disposition: the biological fate of chemicals2011

Identification of cytochrome P450 oxidoreductase gene variants that are significantly associated with the interindividual variations in warfarin maintenance dose.

Xiuling Zhang, Lei Li, Xinxin Ding, Laurence S Kaminsky

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Drug metabolism and disposition: the biological fate of chemicals, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed, 2 pooled it
7.7field-weighted citation impact, top 3% 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

23 citing papers in PubMed, 2 syntheses or guidelines pooled it, 46 citations in OpenAlex.

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  17. Pharmacogenomics of human P450 oxidoreductase.Frontiers in pharmacology · 2014
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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

4 authors at 2 institutions in 1 country.

Xiuling ZhangWadsworth Center, New York State Department of Health, Albany, NY 12201-0509, USA.
Lei Li
Xinxin Ding
Laurence S Kaminsky
Wadsworth Center · USNew York State Department of Health · US

Funding

Human CYP2A and respiratory tract xenobiotic toxicityR01CA092596 · NCI · WADSWORTH CENTER · PI DING, XINXIN · 2003 to 2020
$6.1M
NCI NIH HHS CA092596NCI NIH HHS R01 CA092596
6 · The paper itself

Abstract

Cytochrome P450 oxidoreductase (POR) is required for drug metabolism by all microsomal cytochrome P450 enzymes. The aim of this study was to investigate whether any of the common single nucleotide polymorphisms (SNPs) in the POR gene and its flanking intergenic sequences correlate with interindividual variations in the warfarin maintenance dose (which is determined partly by rates of warfarin metabolism) in patients undergoing anticoagulation therapy. Warfarin dose and patients' demographic and clinical information were collected from 124 patients, who had attained a stable warfarin dose while receiving treatment at the Stratton VA Medical Center. Genomic DNAs were isolated from blood samples and were genotyped for 15 SNPs (including 10 SNPs on the POR gene). Association analysis was performed on 122 male patients by linear regression. Simple regression analysis revealed that vitamin K epoxide reductase complex subunit 1 (VKORC1) -1639A>G, CYP2C9*2, CYP2C9*3, age, and chronic aspirin therapy were significantly associated with warfarin dose. In contrast, multiple regression analysis revealed that, in addition to several known factors contributing to the variations in warfarin maintenance dose (VKORC1 -1639A>G, CYP2C9*2, CYP2C9*3, CYP4F2 rs2108622, and chronic aspirin therapy), three common POR SNPs (-173C>A, -208C>T, and rs2868177) were also significantly associated with variations in warfarin maintenance dose. These results indicate, for the first time, that three common SNPs in the POR gene may contribute to the interindividual variability in warfarin maintenance dose. Further studies on functional characterization of the POR SNPs identified, including their impact on the in vivo metabolism of additional drugs, are needed.

Indexed as

Polymorphism, Single NucleotideAdultAgedAged, 80 and overAnticoagulantsAryl Hydrocarbon HydroxylasesAspirinCytochrome P-450 CYP2C9Cytochrome P-450 Enzyme SystemCytochrome P450 Family 4Dose-Response Relationship, DrugGene FrequencyGenotypeHumansLinear ModelsMaleAnticoagulantsAryl Hydrocarbon HydroxylasesAspirinCYP2C9 protein, humanCYP4F2 protein, humanCytochrome P-450 CYP2C9Cytochrome P-450 Enzyme SystemCytochrome P450 Family 4Mixed Function OxygenasesVitamin K Epoxide ReductasesVKORC1 protein, humanWarfarin

Identifiers

PMID21562147
PMCPMC3141882
OpenAlexW2129715675

What OpenQuestion holds

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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.