title: PXR variants and artemisinin use in Vietnamese subjects: frequency distribution and impact on the interindividual variability of CYP3A induction by artemisinin.
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.
authors.affiliation: Dr. Margarete Fischer Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany. rita.piedade@ki.se
authors.forename: Rita
authors.initials: R
authors.lastname: Piedade
authors.forename: Elke
authors.initials: E
authors.lastname: Schaeffeler
authors.forename: Stefan
authors.initials: S
authors.lastname: Winter
authors.forename: Sara
authors.initials: S
authors.lastname: Asimus
authors.forename: Matthias
authors.initials: M
authors.lastname: Schwab
authors.forename: Michael
authors.initials: M
authors.lastname: Ashton
authors.forename: Oliver
authors.initials: O
authors.lastname: Burk
authors.forename: José P
authors.initials: JP
authors.lastname: Gil
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000483:Alleles; D000962:Antimalarials / Q000494:pharmacology*; D037621:Artemisinins / Q000494:pharmacology*; D051544:Cytochrome P-450 CYP3A / Q000096:biosynthesis* / Q000235:genetics; D017931:DNA Primers; D004790:Enzyme Induction / Q000187:drug effects; D005787:Gene Frequency; D014644:Genetic Variation; D006801:Humans; D004364:Pharmaceutical Preparations / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid / Q000187:drug effects / Q000235:genetics*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014744:Vietnam / Q000453:epidemiology
chemical_list: D020413:3' Untranslated Regions; D000962:Antimalarials; D037621:Artemisinins; D017931:DNA Primers; D004364:Pharmaceutical Preparations; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid; C031327:artemisinin; D051544:Cytochrome P-450 CYP3A