Evidence map›Paper›PMID 25979262›Full record

ArticleDrug metabolism and disposition: the biological fate of chemicals2015

Variability in Expression of CYP3A5 in Human Fetal Liver.

Carrie A Vyhlidal, Robin E Pearce, Roger Gaedigk, Justina C Calamia, Diana L Shuster, Kenneth E Thummel, J Steven Leeder

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

Article in Drug metabolism and disposition: the biological fate of chemicals, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
3.6field-weighted citation impact, top 9% 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

15 citing papers in PubMed, 21 citations in OpenAlex.

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  9. Ontogeny of Drug-Metabolizing Enzymes.Methods in molecular biology (Clifton, N.J.) · 2021
    Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

Carrie A VyhlidalDivision of Clinical Pharmacology, Toxicology and Therapeutic Innovation, Department of Pediatrics, Children's Mercy Hospital, Kansas City, Missouri (C.A.V., R.E.P., R.G., J.S.L.); Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, Washington (J.C.C., D.L.S., K.E.T.) cvyhlidal@cmh.edu.
Robin E PearceDivision of Clinical Pharmacology, Toxicology and Therapeutic Innovation, Department of Pediatrics, Children's Mercy Hospital, Kansas City, Missouri (C.A.V., R.E.P., R.G., J.S.L.); Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, Washington (J.C.C., D.L.S., K.E.T.).
Roger GaedigkDivision of Clinical Pharmacology, Toxicology and Therapeutic Innovation, Department of Pediatrics, Children's Mercy Hospital, Kansas City, Missouri (C.A.V., R.E.P., R.G., J.S.L.); Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, Washington (J.C.C., D.L.S., K.E.T.).
Justina C CalamiaDivision of Clinical Pharmacology, Toxicology and Therapeutic Innovation, Department of Pediatrics, Children's Mercy Hospital, Kansas City, Missouri (C.A.V., R.E.P., R.G., J.S.L.); Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, Washington (J.C.C., D.L.S., K.E.T.).
Diana L ShusterDivision of Clinical Pharmacology, Toxicology and Therapeutic Innovation, Department of Pediatrics, Children's Mercy Hospital, Kansas City, Missouri (C.A.V., R.E.P., R.G., J.S.L.); Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, Washington (J.C.C., D.L.S., K.E.T.).
Kenneth E ThummelDivision of Clinical Pharmacology, Toxicology and Therapeutic Innovation, Department of Pediatrics, Children's Mercy Hospital, Kansas City, Missouri (C.A.V., R.E.P., R.G., J.S.L.); Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, Washington (J.C.C., D.L.S., K.E.T.).
J Steven LeederDivision of Clinical Pharmacology, Toxicology and Therapeutic Innovation, Department of Pediatrics, Children's Mercy Hospital, Kansas City, Missouri (C.A.V., R.E.P., R.G., J.S.L.); Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, Washington (J.C.C., D.L.S., K.E.T.).
University of Washington · USChildren's Mercy Hospital · US

Funding

Pharmacogenetics in Rural and Underserved PopulationsU01GM092676 · NIGMS · UNIVERSITY OF WASHINGTON · PI BURKE, WYLIE G., THUMMEL, KENNETH E. · 2010 to 2014
$9.9M
NIGMS NIH HHS U01 GM092676
6 · The paper itself

Abstract

Members of the cytochrome P450 3A (CYP3A) subfamily of drug metabolizing enzymes exhibit developmental changes in expression in human liver characterized by a transition between CYP3A7 and CYP3A4 over the first few years of life. In contrast, the developmental expression of CYP3A5 is less well understood due to polymorphic expression of the enzyme in human tissues as a result of the prevalence of the CYP3A5*3 allele, which leads to alternative splicing. We further explored the expression of CYP3A5 and the impact of alternative splicing on the variability of CYP3A5 functional activity in a large bank of human prenatal liver samples (7 to 32 weeks of age postconception). The expression of normally spliced CYP3A5 mRNA in all human fetal liver samples varied 235-fold whereas CYP3A5 SV1 mRNA was only detected in fetal liver samples with at least one CYP3A5*3 allele. Formation of 1'-OH midazolam (MDZ) varied 79-fold, and the ratio of 1'-OH MDZ to 4-OH MDZ varied 8-fold and depended on the presence or absence of the CYP3A5*3 allele. Formation of 4-OH MDZ was significantly associated with 1'-OH MDZ (r(2) = 0.76, P < 0.0001) but varied (36-fold) independently of CYP3A5 genotype or expression. The substantial interindividual variability that remains even after stratification for CYP3A5 genotype suggests that factors such as environmental exposure and epigenetic alterations act in addition to genetic variation to contribute to the variability of CYP3A5 expression in human prenatal liver.

Indexed as

AdultAllelesBiotransformationCytochrome P-450 CYP3AEpigenesis, GeneticFemaleFetusGenetic VariationGenotypeGestational AgeHumansHydroxylationLiverMicrosomes, LiverMidazolamPregnancyCYP3A5 protein, humanCytochrome P-450 CYP3AMidazolamRNA, Messenger

Identifiers

PMID25979262
PMCPMC6067386
OpenAlexW1862656882

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.