TY - JOUR
T1 - Impact of cytochrome P450 3A and ATP-binding cassette subfamily B member 1 polymorphisms on tacrolimus dose-adjusted trough concentrations among Korean renal transplant recipients
AU - Cho, J. H.
AU - Yoon, Y. D.
AU - Park, J. Y.
AU - Song, E. J.
AU - Choi, J. Y.
AU - Yoon, S. H.
AU - Park, S. H.
AU - Kim, Y. L.
AU - Kim, C. D.
PY - 2012/1
Y1 - 2012/1
N2 - Background: Tacrolimus is a substrate of cytochrome P450 3A (CYP3A) and P-glycoprotein (P-gp), encoded by the CYP3A and ATP-binding cassette subfamily B member 1 (ABCB1) genes, respectively. This study was aimed to investigate the impact of CYP3A and ABCB1 polymorphisms on the tacrolimus pharmacokinetics and clinical outcomes in Korean renal transplant recipients. Methods: We analyzed data from a cohort of 70 renal transplant recipients receiving tacrolimus. CYP3A4 (*)4, CYP3A4 (*)5, CYP3A4 (*)18, CYP3A5 (*)3, ABCB1 C1236>T, ABCB1 G2677>T/A, and ABCB1 C3435>T polymorphisms were genotyped and correlated to dose-adjusted tacrolimus trough concentration at months 1, 3, 6, and 12 after transplantation. Results: Patients with the CYP3A5 (*)3 alleles showed higher dose-adjusted tacrolimus concentrations for 12 months and higher trough levels until 6 months after transplantation. ABCB1 polymorphisms and haplotypes were not associated with tacrolimus concentrations. In a multivariate analysis, the presence of ≥1 CYP3A5 (*)3 allele was a significant independent variable affecting dose-adjusted tacrolimus concentrations. Glomerular filtration rate, acute rejection, opportunistic infection, and graft survival were not affected by CYP3A5 polymorphisms. Calcineurin inhibitor toxicity, which showed higher tendency in patients with CYP3A5 (*)1 alleles, might be associated with higher tacrolimus dose per kilogram. Conclusions: The CYP3A5 genotype is a major factor in determining the dose requirement of tacrolimus, and genotyping may be of value in individualization of immunosuppressive therapy of renal transplant patients.
AB - Background: Tacrolimus is a substrate of cytochrome P450 3A (CYP3A) and P-glycoprotein (P-gp), encoded by the CYP3A and ATP-binding cassette subfamily B member 1 (ABCB1) genes, respectively. This study was aimed to investigate the impact of CYP3A and ABCB1 polymorphisms on the tacrolimus pharmacokinetics and clinical outcomes in Korean renal transplant recipients. Methods: We analyzed data from a cohort of 70 renal transplant recipients receiving tacrolimus. CYP3A4 (*)4, CYP3A4 (*)5, CYP3A4 (*)18, CYP3A5 (*)3, ABCB1 C1236>T, ABCB1 G2677>T/A, and ABCB1 C3435>T polymorphisms were genotyped and correlated to dose-adjusted tacrolimus trough concentration at months 1, 3, 6, and 12 after transplantation. Results: Patients with the CYP3A5 (*)3 alleles showed higher dose-adjusted tacrolimus concentrations for 12 months and higher trough levels until 6 months after transplantation. ABCB1 polymorphisms and haplotypes were not associated with tacrolimus concentrations. In a multivariate analysis, the presence of ≥1 CYP3A5 (*)3 allele was a significant independent variable affecting dose-adjusted tacrolimus concentrations. Glomerular filtration rate, acute rejection, opportunistic infection, and graft survival were not affected by CYP3A5 polymorphisms. Calcineurin inhibitor toxicity, which showed higher tendency in patients with CYP3A5 (*)1 alleles, might be associated with higher tacrolimus dose per kilogram. Conclusions: The CYP3A5 genotype is a major factor in determining the dose requirement of tacrolimus, and genotyping may be of value in individualization of immunosuppressive therapy of renal transplant patients.
UR - http://www.scopus.com/inward/record.url?scp=84863357335&partnerID=8YFLogxK
U2 - 10.1016/j.transproceed.2011.11.004
DO - 10.1016/j.transproceed.2011.11.004
M3 - Article
C2 - 22310591
AN - SCOPUS:84863357335
SN - 0041-1345
VL - 44
SP - 109
EP - 114
JO - Transplantation Proceedings
JF - Transplantation Proceedings
IS - 1
ER -