Retracted: Polymorphisms of tumor necrosis factor-alpha, interleukin-10, cytochrome P450 3A5 and ABCB1 in Chinese liver transplant patients treated with immunosuppressant tacrolimus.
Cytokine production in the host immune response after transplantation may contribute to the variable CYP3A-dependent drug disposition. We investigated the effect of TNF-alpha, IL-10, CYP3A5 and ABCB1 polymorphisms on immunosuppressant tacrolimus pharmacokinetics in liver transplant patients.



Genetic polymorphisms in TNF-alpha, IL-10, CYP3A5 and ABCB1 were studied in 70 liver transplant recipients and 70 donors. Tacrolimus dosage and blood concentration were investigated at 1, 2 and 3 weeks after transplantation.



The IL-10 G-1082A polymorphism in recipients was significantly associated with tacrolimus concentration/dose (C/D) ratios (IL-10-1082GG < GA < AA) within the first 3weeks posttransplantation (P < 0.05). Recipients with the capacity for low IL-10 production (-1082AA) carrying CYP3A5 non-expressor (CYP3A5()3/()3) liver had the highest C/D ratios (mean: 172.4, 161.7, 160.3 for 1, 2 and 3 weeks posttransplantation, respectively), whereas recipients with intermediate or high production of IL-10 (-1082GA or GG) engrafted with CYP3A5 expressor (CYP3A5()1 carrier) liver were found to have the lowest ratios (96.4, 78.0 and 75.4, respectively, P < 0.01).



The IL-10 G-1082A and CYP3A5()3 polymorphisms may influence the interindividual variability of tacrolimus pharmacokinetics in Chinese liver transplant patients. This finding provided a new interpretation for the variable immunosuprressant disposition after transplantation.
Li
Dan
D
Department of Pharmacology, Basic Medical School, Beijing University, Beijing, China.
Zhu
Ji-Ye
JY
Gao
Jie
J
Wang
Xin
X
Lou
Ya-Qing
YQ
Zhang
Guo-Liang
GL
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000328:Adult; D000368:Aged; D044466:Asian People; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics; D016753:Interleukin-10 / Q000235:genetics*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D010599:Pharmacokinetics; D020641:Polymorphism, Single Nucleotide / Q000502:physiology*; D012189:Retrospective Studies; D016559:Tacrolimus / Q000493:pharmacokinetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D007166:Immunosuppressive Agents; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D003577:Cytochrome P-450 Enzyme System; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; D016559:Tacrolimus