Evidence map›Paper›PMID 26779253›Full record

ArticleFrontiers in genetics2015

An Expanded Analysis of Pharmacogenetics Determinants of Efavirenz Response that Includes 3'-UTR Single Nucleotide Polymorphisms among Black South African HIV/AIDS Patients.

Marelize Swart, Jonathan Evans, Michelle Skelton, Sandra Castel, Lubbe Wiesner, Peter J Smith, Collet Dandara

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PubMed Full text at PMC Publisher
In one paragraph

Article in Frontiers in genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
–field-weighted citation impact
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

19 citing papers in PubMed.

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  15. Variation in CYP2A6 Activity and Personalized Medicine.Journal of personalized medicine · 2017
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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

7 authors.

Marelize SwartDivision of Human Genetics, Department of Pathology and Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town Cape Town, South Africa.
Jonathan EvansDivision of Human Genetics, Department of Pathology and Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town Cape Town, South Africa.
Michelle SkeltonDivision of Human Genetics, Department of Pathology and Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town Cape Town, South Africa.
Sandra CastelDivision of Clinical Pharmacology, Faculty of Health Sciences, University of Cape Town Cape Town, South Africa.
Lubbe WiesnerDivision of Clinical Pharmacology, Faculty of Health Sciences, University of Cape Town Cape Town, South Africa.
Peter J SmithDivision of Clinical Pharmacology, Faculty of Health Sciences, University of Cape Town Cape Town, South Africa.
Collet DandaraDivision of Human Genetics, Department of Pathology and Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town Cape Town, South Africa.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionEfavirenz (EFV) is a non-nucleoside reverse transcriptase inhibitor prescribed as part of first-line highly active antiretroviral therapy (HAART) in South Africa. Despite administration of fixed doses of EFV, inter-individual variability in plasma concentrations has been reported. Poor treatment outcomes such as development of adverse drug reactions or treatment failure have been linked to EFV plasma concentrations outside the therapeutic range (1-4 μg/mL) in some studies. The drug metabolizing enzyme (DME), CYP2B6, is primarily responsible for EFV metabolism with minor contributions by CYP1A2, CYP2A6, CYP3A4, CYP3A5, and UGT2B7. DME coding genes are also regulated by microRNAs through targeting the 3'-untranslated region. Expanded analysis of 30 single nucleotide polymorphisms (SNPs), including those in the 3'-UTR, was performed to identify pharmacogenetics determinants of EFV plasma concentrations in addition to CYP2B6 c.516G>T and c.983T>C SNPs.

methodsSNPs in CYP1A2, CYP2B6, UGT2B7, and NR1I2 (PXR) were selected for genotyping among 222 Bantu-speaking South African HIV-infected patients receiving EFV-containing HAART. This study is a continuation of earlier pharmacogenetics studies emphasizing the role of genetic variation in the 3'-UTR of genes which products are either pharmacokinetic or pharmacodynamic targets of EFV.

resultsDespite evaluating thirty SNPs, CYP2B6 c.516G>T and c.983T>C SNPs remain the most prominent predictors of EFV plasma concentration.

conclusionWe have shown that CYP2B6 c.516G>T and c.983T>C SNPs are the most important predictors of EFV plasma concentration after taking into account all other SNPs, including genetic variation in the 3'-UTR, and variables affecting EFV metabolism.

Indexed as

3′-UTRefavirenzHIV/AIDSpharmacogeneticssensitivitysingle nucleotide polymorphismSouth Africaspecificity

Identifiers

PMID26779253
PMCPMC4703773

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