Received for publication June 28, 2007.
Revised October 8, 2007.
Accepted for publication October 11, 2007.

Transcription factors and drug metabolizing enzymes genes expression in lymphocytes from human healthy subjects

Abstract

We aimed to measure simultaneously in healthy subjects lymphocytes the expression of drug metabolizing enzymes (DME) and transcription factors (TF) with high importance in cardiovascular physiopathology. RNA was isolated from peripheral blood mononuclear cells (PBMC) of twenty subjects from the Stanislas Cohort. We used a microarray approach to measure sixteen DME and thirteen TF. Cytochromes P450 including CYP2C19, CYP2C9, CYP2J2, CYP2D6, CYP1A1, CYP4F2, CYP4A11, CYP2E1, CYP11B2, CYP2C18 and CYP2A6 were expressed in all subjects. CYP3A4 and CYP3A5 were not expressed. GST were expressed but GSTM1 only in some subjects. PXR, MEF2A, VDR, LXR, AHR, TCF7, CAR and ARNT were expressed in the majority of the subjects. GR, PPAR, and LXR were expressed only in some individuals. PPAR mRNA was found in one subject only and FXR was not expressed. In addition, we found significant correlations between the expression of AHR, ARNT and CYP1A1 and between PXR and CYP involved in leukotrienes metabolism (CYP2C, CYP4F2, CYP4A11, CYP2J2 and CYP11B2). We describe here for the first time the presence of the majority of TF and DME in PBMC of healthy subjects without prior induction. The expression of these genes in lymphocytes could be a useful tool for further studying the physiological and pathological variations of DME and TF related to drug intake, to environment and to cardiovascular metabolic cycles.

Key words: Ah receptor, CYP expression, extrahepatic drug metabolism, human CYP enzymes, microarrays, PXR, regulation of gene expression