Impact of the haplotypes of the human pregnane X receptor gene on the basal and St John's wort-induced activity of cytochrome P450 3A4 enzyme

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT - Human pregnane X receptor (PXR/NR1I2) is a key regulator of cytochrome P450 3A4. - To date, there are 198 reported SNPs for the human PXR/NR1I2 gene. - Some of these SNPs are found to affect the inducing ability of PXR to CYP3A4. WHAT THIS STUDY ADDS - This study, for the first time, has investigated the effect of PXR haplotype on basal and St John's wort-induced CYP3A4 activity in humans. - H1/H1 of the PXR gene had weaker basal transcriptional activity but greater inducible transcriptional activity to CYP3A4 than H1/H2 and H2/H2.