Evidence map›Paper›PMID 38050015›Full record

ArticleDrug metabolism and disposition: the biological fate of chemicals2024

Novel Independent Trans- and Cis-Genetic Variants Associated with CYP2D6 Expression and Activity in Human Livers.

Dylan Smith, Bing He, Jian Shi, Hao-Jie Zhu, Xinwen Wang

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

Article in Drug metabolism and disposition: the biological fate of chemicals, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.5field-weighted citation impact, top 32% 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

1 citing paper in PubMed, 2 citations in OpenAlex.

  1. Article
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

5 authors at 1 institution in 1 country.

Dylan SmithDepartment of Pharmaceutical Sciences, Northeast Ohio Medical University, Rootstown, Ohio (D.S., X.W.); Department of Clinical Pharmacy, University of Michigan, Ann Arbor, Michigan (H.-J.Z.); Department of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, Michigan (B.H.); and Bristol Myers Squibb, Lawrence Township, New Jersey (J.S.).
Bing HeDepartment of Pharmaceutical Sciences, Northeast Ohio Medical University, Rootstown, Ohio (D.S., X.W.); Department of Clinical Pharmacy, University of Michigan, Ann Arbor, Michigan (H.-J.Z.); Department of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, Michigan (B.H.); and Bristol Myers Squibb, Lawrence Township, New Jersey (J.S.).
Jian ShiDepartment of Pharmaceutical Sciences, Northeast Ohio Medical University, Rootstown, Ohio (D.S., X.W.); Department of Clinical Pharmacy, University of Michigan, Ann Arbor, Michigan (H.-J.Z.); Department of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, Michigan (B.H.); and Bristol Myers Squibb, Lawrence Township, New Jersey (J.S.).
Hao-Jie ZhuDepartment of Pharmaceutical Sciences, Northeast Ohio Medical University, Rootstown, Ohio (D.S., X.W.); Department of Clinical Pharmacy, University of Michigan, Ann Arbor, Michigan (H.-J.Z.); Department of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, Michigan (B.H.); and Bristol Myers Squibb, Lawrence Township, New Jersey (J.S.) xwang2@neomed.edu hjzhu@umich.med.edu.ORCID 0000-0002-2248-4419
Xinwen WangDepartment of Pharmaceutical Sciences, Northeast Ohio Medical University, Rootstown, Ohio (D.S., X.W.); Department of Clinical Pharmacy, University of Michigan, Ann Arbor, Michigan (H.-J.Z.); Department of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, Michigan (B.H.); and Bristol Myers Squibb, Lawrence Township, New Jersey (J.S.) xwang2@neomed.edu hjzhu@umich.med.edu.
University of Michigan · US

Funding

Carboxylesterase 1 Plasma Biomarker for Precision PharmacotherapyR01GM144401 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ZHU, HAOJIE · 2022 to 2024
$936k
NIGMS NIH HHS R01 GM144401
6 · The paper itself

Abstract

Cytochrome P450 2D6 (CYP2D6) is a critical hepatic drug-metabolizing enzyme in humans, responsible for metabolizing approximately 20%-25% of commonly used medications such as codeine, desipramine, fluvoxamine, paroxetine, and tamoxifen. The CYP2D6 gene is highly polymorphic, resulting in substantial interindividual variability in its catalytic function and the pharmacokinetics and therapeutic outcomes of its substrate drugs. Although many functional CYP2D6 variants have been discovered and validated, a significant portion of the variability in the expression and activity of CYP2D6 remains unexplained. In this study, we performed a genome-wide association study (GWAS) to identify novel variants associated with CYP2D6 protein expression in individual human livers, followed by a conditional analysis to control for the effect of functional CYP2D6 star alleles. We also examined their impact on hepatic CYP2D6 activity. Genotyping on a genome-wide scale was achieved using the Illumina Multi-Ethnic Genotyping Array (MEGA). A data-independent acquisition (DIA)-based proteomics method was used to quantify CYP2D6 protein concentrations. CYP2D6 activity was determined by measuring the dextromethorphan O-demethylation in individual human liver s9 fractions. The GWAS identified 44 single nuclear polymorphisms (SNPs) that are significantly associated with CYP2D6 protein expressions with a

Indexed as

Cytochrome P-450 CYP2D6Genome-Wide Association StudyFluvoxamineHumansLiverParoxetineCYP2D6 protein, humanCytochrome P-450 CYP2D6FluvoxamineParoxetine

Identifiers

PMID38050015
PMCPMC10801631
OpenAlexW4389132632

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.