Impact of the CYP3A5, CYP3A4, COMT, IL-10 and POR genetic polymorphisms on tacrolimus metabolism in Chinese renal transplant recipients.
Tacrolimus is a widely used immunosuppressive drug for preventing the rejection of solid organ transplants. The efficacy of tacrolimus shows considerable variability, which might be related to genetic variation among recipients. We conducted a retrospective study of 240 Chinese renal transplant recipients receiving tacrolimus as immunosuppressive drug. The retrospective data of all patients were collected for 40 days after transplantation. Seventeen SNPs of CYP3A5, CYP3A4, COMT, IL-10 and POR were identified by the SNaPshot assay. Tacrolimus blood concentrations were obtained on days 1-3, days 6-8 and days 12-14 after transplantation, as well as during the period of the predefined therapeutic concentration range. Kruskal-Wallis test was used to examine the effect of genetic variation on the tacrolimus concentration/dose ratio (C 0/D) at different time points. Chi-square test was used to compare the proportions of patients who achieved the target C 0 range in the different genotypic groups at weeks 1, 2, 3 and 4 after transplantation. After correction for multiple testing, there was a significant association of C 0/D with CYP3A5*3, CYP3A4*1G and CYP3A4 rs4646437 T>C at different time points after transplantation. The proportion of patients in the IL-10 rs1800871-TT group who achieved the target C 0 range was greater (p = 0.004) compared to the IL-10 rs1800871-CT and IL-10 rs1800871-CC groups at week 3 after transplantation. CYP3A5*3, CYP3A4 *1G, CYP3A4 rs4646437 T>C and IL-10 rs1800871 C>T might be potential polymorphisms affecting the interindividual variability in tacrolimus metabolism among Chinese renal transplant recipients.
Department of Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, PR China.
Chuan-Jiang
CJ
Li
Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, PR China.
Liang
L
Li
Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, PR China.
Li
L
Lin
Department of Clinical Laboratory, Nanfang Hospital, Southern Medical University, Guangzhou, PR China.
Hai-Xia
HX
Jiang
Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, PR China.
Ze-Yan
ZY
Zhong
Department of Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, PR China.
Wei-Mo
WM
Li
College of Pharmacy, University of Cincinnati Academic Health Centre, Cincinnati, Ohio, United States of America.
Yan-Jun
YJ
Zhang
Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou, PR China.
Ping
P
Zheng
Department of Biostatistics, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, PR China.
Xu-Hui
XH
Tan
Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, PR China.
Lin
L
Zhou
D000328:Adult; D044466:Asian People / Q000235:genetics; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000378:metabolism / Q000494:pharmacology; D016753:Interleukin-10 / Q000235:genetics*; D016030:Kidney Transplantation; D008297:Male; D009251:NADPH-Ferrihemoprotein Reductase / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012189:Retrospective Studies; D016559:Tacrolimus / Q000378:metabolism* / Q000494:pharmacology
C508609:IL10 protein, human; D007166:Immunosuppressive Agents; D016753:Interleukin-10; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D009251:NADPH-Ferrihemoprotein Reductase; C588010:COMT protein, human; D002394:Catechol O-Methyltransferase; D016559:Tacrolimus