CYP2D6 mRNA expression in circulating peripheral blood mononuclear cells correlates with in vivo debrisoquine hydroxylase activity in extensive metabolizers.
Extensive metabolizers of drugs which are oxidized by cytochrome P450s show wide interindividual variability in drug metabolism. Elucidation of the relationship between specific P450 isozyme mRNA expression and variability in metabolism of specific drugs could improve understanding of the molecular mechanism involved. In this study, a novel non-radiometric reverse transcription polymerase chain reaction based assay was used to quantify CYP2D6 mRNA levels in peripheral blood mononuclear cells in twelve human volunteers who were phenotyped as extensive metabolizers of debrisoquine. We report a significant correlation (r=0.724, p= 0.008) between CYP2D6 mRNA levels in circulating peripheral blood mononuclear cells and the in vivo debrisoquine recovery ratio. This suggests that interindividual variability in extensive metabolizers could be related, in part, to differences in gene expression. Circulating peripheral blood mononuclear cells can provide an accessible ex vivo measure of this phenomenon.
Carcillo
J A
JA
Department of Anesthesiology, Graduate School of Public Health, University of Pittsburgh, PA, USA.
Parise
R A
RA
Adedoyin
A
A
Frye
R
R
Branch
R A
RA
Romkes
M
M
D000199:Actins / Q000096:biosynthesis; D000328:Adult; D000368:Aged; D019389:Cytochrome P-450 CYP2D6 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000201:enzymology / Q000378:metabolism*; D009369:Neoplasms / Q000201:enzymology; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000302:isolation & purification
D000199:Actins; D012333:RNA, Messenger; D019389:Cytochrome P-450 CYP2D6