Gene expression of P-glycoprotein and cytochrome P450 3A4 in peripheral blood mononuclear cells and correlation with expression in liver.
Long-term immunosuppression in renal transplant recipients generally includes calcineurin inhibitors (CNIs), which demonstrate marked interindividual diversity and a narrow therapeutic range. In the clinical setting, it is important to reach therapeutic drug concentrations to prevent allograft rejection. The same immunosuppressant dosage leads to different drug concentrations. Therefore, we investigated factors that influence the metabolism of immunosuppressant agents. The CNIs are substrates of cytochrome P450 (CYP450) and P-glycoprotein. The CYP450 3A genotype significantly influences CNI concentration. Differences in expression of these proteins may explain interindividual pharmacokinetic variations. However, it is risky and impractical to obtain specimens from the liver in renal transplant recipients. Therefore, we investigated the correlation of gene expression between peripheral blood mononuclear cells (PBMCs) and liver parenchyma. We observed that the correlation of relative P-glycoprotein gene expression between PBMCs and liver is not significant (r2=0.03; P=.65). In addition, the correlation of CYP450 3A4 gene expression between PBMCs and liver is not strong (r2=0.23; P=.42). The expression level of CYP450 3A5 is too low to be detected in the sample from PBMCs.
Lee
C-Y
CY
Department of Surgery, National Taiwan University Hospital, and Institute of Molecular Medicine, National Taiwan University, Taipei, Taiwan.
Lai
T-Y
TY
Wu
Y-M
YM
Hu
R-H
RH
Lee
P-H
PH
Hsu
L-C
LC
Tsai
M-K
MK
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000097:blood / Q000235:genetics*; D000328:Adult; D051544:Cytochrome P-450 CYP3A / Q000097:blood / Q000235:genetics*; D017931:DNA Primers; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D015971:Gene Expression Regulation, Enzymologic; D006498:Hepatectomy; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000502:physiology; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D016031:Liver Transplantation / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012044:Regression Analysis
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D017931:DNA Primers; D018076:DNA, Complementary; D012313:RNA; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human