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

Piedade, Rita; Schaeffeler, Elke; Winter, Stefan; Asimus, Sara; Schwab, Matthias; Ashton, Michael; Burk, Oliver; Gil, José Pedro

http://hdl.handle.net/10400.1/11104

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Abstract(s)

Artemisinins induce drug metabolism through the activation of the pregnane X receptor (PXR) in vitro. Here, we report the re-sequencing 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.

Keywords

Pregnane-X-receptor Single-nucleotide polymorphisms Constitutive-androstane-receptor Inflammatory-bowel-disease Falciparum-malaria Gene Association Pharmacokinetics Pharmacogenetics Cytochrome-P450