Evidence map›Paper›PMID 18825162›Full record

ArticleThe pharmacogenomics journal2009

Prediction of CYP3A4 enzyme activity using haplotype tag SNPs in African Americans.

M A Perera, R K Thirumaran, N J Cox, S Hanauer, S Das, C Brimer-Cline, V Lamba, E G Schuetz, M J Ratain, A Di Rienzo

Open access · greenAbstract read
In one paragraph

Article in The pharmacogenomics journal, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
4.2field-weighted citation impact, top 7% 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

12 citing papers in PubMed, 22 citations in OpenAlex.

  1. Trial
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  4. Article
  5. Role of Chromatin Structural Changes in Regulating Human CYP3A Ontogeny.Drug metabolism and disposition: the biological fate of chemicals · 2016
    Article
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  8. Review
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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

10 authors at 2 institutions in 1 country.

M A PereraCommittee on Clinical Pharmacology and Pharmacogenomics, Division of Biological Sciences, University of Chicago, Chicago, IL, USA. mperera@bsd.uchicago.edu
R K Thirumaran
N J Cox
S Hanauer
S Das
C Brimer-Cline
V Lamba
E G Schuetz
M J Ratain
A Di Rienzo
University of Chicago · USSt. Jude Children's Research Hospital · US

Funding

Whole GenomeU01GM061393 · NIGMS · UNIVERSITY OF CHICAGO · PI COX, NANCY J, DOLAN, MARY EILEEN · 2000 to 2014
$39.0M
CLINICAL THERAPEUTICST32GM007019 · NIGMS · UNIVERSITY OF CHICAGO · PI Peter Hugh O'Donnell, MARK J RATAIN · 1985 to 2026
$8.7M
PXR: Regulation and PharmacogenomicsR01GM060346 · NIGMS · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI SCHUETZ, ERIN G · 2000 to 2007
$2.2M
The implementation of a pharmacogenomics-based algorithm for warfarin dosingK23HL089808 · NHLBI · UNIVERSITY OF CHICAGO · PI PERERA, MINOLI A · 2009 to 2013
$601k
NHLBI NIH HHS K23 HL089808NIGMS NIH HHS GM07019NIGMS NIH HHS GM60346NIGMS NIH HHS GM61393NIGMS NIH HHS R01 GM060346NIGMS NIH HHS T32 GM007019NIGMS NIH HHS U01 GM061393
6 · The paper itself

Abstract

The CYP3A locus encodes hepatic enzymes that metabolize many clinically used drugs. However, there is marked interindividual variability in enzyme expression and clearance of drugs metabolized by these enzymes. We utilized comparative genomics and computational prediction of transcriptional factor binding sites to evaluate regions within CYP3A that were most likely to contribute to this variation. We then used a haplotype tagging single-nucleotide polymorphisms (htSNPs) approach to evaluate the entire locus with the fewest number of maximally informative SNPs. We investigated the association between these htSNPs and in vivo CYP3A enzyme activity using a single-point IV midazolam clearance assay. We found associations between the midazolam phenotype and age, diagnosis of hypertension and one htSNP (141689) located upstream of CYP3A4. 141689 lies near the xenobiotic responsive enhancer module (XREM) regulatory region of CYP3A4. Cell-based studies show increased transcriptional activation with the minor allele at 141689, in agreement with the in vivo association study findings. This study marks the first systematic evaluation of coding and noncoding variation that may contribute to CYP3A phenotypic variability.

Indexed as

HaplotypesPolymorphism, Single NucleotideAdultAgedAged, 80 and overBlack or African AmericanCell Line, TumorCytochrome P-450 CYP3AFemaleGene FrequencyHumansLinkage DisequilibriumMaleMidazolamMiddle AgedPredictive Value of TestsCYP3A4 protein, humanCytochrome P-450 CYP3AMidazolam

Identifiers

PMID18825162
PMCPMC2754748
OpenAlexW2051545975

What OpenQuestion holds

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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.