title: Drug metabolizing enzymes and transporters mRNA in peripheral blood mononuclear cells of healthy subjects: biological variations and importance of pre-analytical steps.
abstract: Quantification in peripheral blood mononuclear cells of mRNA of drug metabolizing enzymes or drug targets could give interesting, new information in the field of pharmacogenomics and molecular mechanisms. However, for the interpretation of these data, it is necessary to know mRNA biological variations. In this review, we propose a strategy based on the production and interpretation of clinical chemistry reference values. We discuss the concept of reference values; the necessity to master pre-analytical variations of CYP and ABC transporters; the choice of the analytical methods and of the reference genes; and finally the biological variations themselves. In particular, we focus on the importance of considering homogeneity for age, sex, degree of adiposity, tobacco and alcohol intake, food habits, and drug consumption, including their inductive effects, at the phase of subject recruitment. All this information is useful to define the partition and exclusion factors to obtain mRNA reference limits.
authors.affiliation: Université Henri Poincaré Nancy I, Faculté de Pharmacie, Equipe Génétique Cardiovasculaire, 30 rue Lionnois, 54000 Nancy, France. gerard.siest@pharma.uhp-nancy.fr
authors.forename: Gérard
authors.initials: G
authors.lastname: Siest
authors.forename: Elise
authors.initials: E
authors.lastname: Jeannesson
authors.forename: Jean-Brice
authors.initials: JB
authors.lastname: Marteau
authors.forename: Anastasia
authors.initials: A
authors.lastname: Samara
authors.forename: Michèle
authors.initials: M
authors.lastname: Pfister
authors.forename: Sophie
authors.initials: S
authors.lastname: Visvikis-Siest
mesh_terms: D054316:Biomarkers, Pharmacological / Q000032:analysis*; D019963:Clinical Chemistry Tests / Q000592:standards; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D006801:Humans; D008658:Inactivation, Metabolic / Q000235:genetics*; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000097:blood / Q000235:genetics*; D012333:RNA, Messenger / Q000097:blood; D012016:Reference Values; D012107:Research Design
chemical_list: D054316:Biomarkers, Pharmacological; D026901:Membrane Transport Proteins; D012333:RNA, Messenger; D003577:Cytochrome P-450 Enzyme System