Evidence map›Paper›PMID 36611001›Full record

ArticleThe journal of applied laboratory medicine2023

Potential Impact of Pharmacogenomic Single Nucleotide Variants in a Rural Caucasian Population.

Grace R Williams, Gregory J Tsongalis, Lionel D Lewis, Rachael E Barney, Leanne J Cook, K Aaron Geno, Robert D Nerenz

Open access · greenAbstract read
In one paragraph

Article in The journal of applied laboratory medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

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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

0 citing papers in PubMed, 0 citations in OpenAlex.

No citing paper in PubMed yet.

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

7 authors at 3 institutions in 1 country.

Grace R WilliamsDepartment of Pathology, Virginia Commonwealth University Health System, Richmond, VA, USA.
Gregory J TsongalisDepartment of Pathology and Laboratory Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA.
Lionel D LewisDepartment of Medicine, The Geisel School of Medicine at Dartmouth and Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA.
Rachael E BarneyDepartment of Pathology and Laboratory Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA.
Leanne J CookDepartment of Pathology and Laboratory Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA.
K Aaron GenoDepartment of Pathology, Texas Tech University Health Sciences Center El Paso, El Paso, TX, USA.ORCID 0000-0002-0799-4189
Robert D NerenzDepartment of Pathology and Laboratory Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA.
Dartmouth–Hitchcock Medical Center · USTexas Tech University · USVirginia Commonwealth University · US

Funding

Translational Engineering in Cancer (TEC)P30CA023108 · NCI · DARTMOUTH COLLEGE · PI Steven D Leach · 1985 to 2026
$91.3M
NCI NIH HHS P30 CA023108
6 · The paper itself

Abstract

backgroundIn the US adverse drug reactions (ADRs) are estimated to cause 100 000 fatalities and cost over $136 billion annually. A patient's genes play a significant role in their response to a drug. Pharmacogenomics aims to optimize drug choice and dose for individual patients by characterizing patients' pharmacologically relevant genes to identify variants of known impact.

methodsDNA was extracted from randomly selected remnant whole blood samples from Caucasian patients with previously performed complete blood counts. Samples were genotyped by mass spectrometry using a customized pharmacogenomics panel. A third-party result interpretation service used genotypic results to predict likely individual responses to frequently prescribed drugs.

resultsComplete genotypic and phenotypic calls for all tested Cytochrome P450 isoenzymes and other genes were obtained from 152 DNA samples. Of these 152 unique genomic DNA samples, 140 had genetic variants suggesting dose adjustment for at least one drug. Cardiovascular and psychiatry drugs had the highest number of recommendations, which included United States Food and Drug Administration warnings for highly prescribed drugs metabolized by CYP2C19, CYP2C9, CYP2D6, HLA-A, and VKORC1.

conclusionsRisk for each drug:gene pairing primarily depends upon the degree of predicted enzyme impairment or activation, width of the therapeutic window, and whether parent compound or metabolite is pharmacologically active. The resulting metabolic variations range from risk of toxicity to therapeutic failure. Pharmacogenomic profiling likely reduces ADR potential by allowing up front drug/dose selection to fit a patient's unique drug-response profile.

Indexed as

Drug-Related Side Effects and Adverse ReactionsPharmacogeneticsCytochrome P-450 CYP2D6GenotypeHumansNucleotidesPharmaceutical PreparationsUnited StatesVitamin K Epoxide ReductasesCytochrome P-450 CYP2D6NucleotidesPharmaceutical PreparationsVitamin K Epoxide ReductasesVKORC1 protein, human

Identifiers

PMID36611001
PMCPMC10539040
OpenAlexW4313702078

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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.