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PXR variants and artemisinin use in Vietnamese subjects: frequency distribution and impact on the interindividual variability of CYP3A induction by artemisinin.

Journal article
Authors Rita Piedade
Elke Schaeffeler
Stefan Winter
Sara Asimus
Matthias Schwab
Michael Ashton
Oliver Burk
José P Gil
Published in Antimicrobial agents and chemotherapy
Volume 56
Issue 4
Pages 2153-7
ISSN 1098-6596
Publication year 2012
Published at Institute of Neuroscience and Physiology, Department of Pharmacology
Pages 2153-7
Language en
Links dx.doi.org/10.1128/AAC.06009-11
Keywords 3' Untranslated Regions, genetics, Alleles, Antimalarials, pharmacology, Artemisinins, pharmacology, Cytochrome P-450 CYP3A, biosynthesis, genetics, DNA Primers, Enzyme Induction, drug effects, Gene Frequency, Genetic Variation, Humans, Pharmaceutical Preparations, metabolism, Polymorphism, Single Nucleotide, Receptors, Steroid, drug effects, genetics, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Vietnam, epidemiology
Subject categories Pharmacy

Abstract

Artemisinins induce drug metabolism through the activation of the pregnane X receptor (PXR) in vitro. Here, we report the resequencing and genotyping of PXR variants in 75 Vietnamese individuals previously characterized for CYP3A enzyme activity after artemisinin exposure. We identified a total of 31 PXR variants, including 5 novel single nucleotide polymorphisms (SNPs), and we identified significantly different allele frequencies relative to other ethnic groups. A trend of significance was observed between the level of CYP3A4 induction by artemisinin and two PXR variants, the 8118C→T (Y328Y) and 10719A→G variants.

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