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

Antimicrob Agents Chemother. 2012 Apr;56(4):2153-7. doi: 10.1128/AAC.06009-11. Epub 2012 Jan 17.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • Alleles
  • Antimalarials / pharmacology*
  • Artemisinins / pharmacology*
  • Cytochrome P-450 CYP3A / biosynthesis*
  • Cytochrome P-450 CYP3A / genetics
  • DNA Primers
  • Enzyme Induction / drug effects
  • Gene Frequency
  • Genetic Variation
  • Humans
  • Pharmaceutical Preparations / metabolism
  • Polymorphism, Single Nucleotide
  • Pregnane X Receptor
  • Receptors, Steroid / drug effects
  • Receptors, Steroid / genetics*
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Vietnam / epidemiology

Substances

  • 3' Untranslated Regions
  • Antimalarials
  • Artemisinins
  • DNA Primers
  • Pharmaceutical Preparations
  • Pregnane X Receptor
  • Receptors, Steroid
  • artemisinin
  • Cytochrome P-450 CYP3A