TY - JOUR
T1 - The effect of CYP3A5 6986A>G and ABCB1 3435C>T on tacrolimus dose-adjusted trough levels and acute rejection rates in renal transplant patients
T2 - A systematic review and meta-analysis
AU - Terrazzino, Salvatore
AU - Quaglia, Marco
AU - Stratta, Piero
AU - Canonico, Pier L.
AU - Genazzani, Armando A.
PY - 2012/8
Y1 - 2012/8
N2 - In the present study, we performed a systematic review and meta-analysis on published data to examine the impact of CYP3A5 6986A>G and ABCB1 3435C>T polymorphisms on tacrolimus dose-adjusted trough levels (C0/D) and acute rejection rates in adult renal transplant patients. Despite the presence of significant heterogeneity in all comparisons, random-effects model showed significantly higher tacrolimus C0/D in CYP3A5*3/*3 compared with CYP3A5* 1 allele carriers, either in the overall analysis and when stratifying for ethnicity or time of post-transplantation (≤1, 3-6, 12-24 months). In contrast, no consistent evidence of an effect of the ABCB1 3435C>T variant was detected on tacrolimus C0/D, except for a modest effect limited to the first month after renal transplantation. In addition, from the current evidence available, CYP3A5 6986A>G and ABCB1 3435C>T polymorphisms seem to have little or no effect on the acute rejection rates in renal transplant patients under immunosuppressive therapy with tacrolimus.
AB - In the present study, we performed a systematic review and meta-analysis on published data to examine the impact of CYP3A5 6986A>G and ABCB1 3435C>T polymorphisms on tacrolimus dose-adjusted trough levels (C0/D) and acute rejection rates in adult renal transplant patients. Despite the presence of significant heterogeneity in all comparisons, random-effects model showed significantly higher tacrolimus C0/D in CYP3A5*3/*3 compared with CYP3A5* 1 allele carriers, either in the overall analysis and when stratifying for ethnicity or time of post-transplantation (≤1, 3-6, 12-24 months). In contrast, no consistent evidence of an effect of the ABCB1 3435C>T variant was detected on tacrolimus C0/D, except for a modest effect limited to the first month after renal transplantation. In addition, from the current evidence available, CYP3A5 6986A>G and ABCB1 3435C>T polymorphisms seem to have little or no effect on the acute rejection rates in renal transplant patients under immunosuppressive therapy with tacrolimus.
KW - ABCB1
KW - CYP3A5
KW - allograft rejection
KW - meta-analysis
KW - pharmacokinetics
KW - polymorphisms
KW - renal transplantation
KW - tacrolimus
UR - http://www.scopus.com/inward/record.url?scp=84863813155&partnerID=8YFLogxK
U2 - 10.1097/FPC.0b013e3283557c74
DO - 10.1097/FPC.0b013e3283557c74
M3 - Review article
SN - 1744-6872
VL - 22
SP - 642
EP - 645
JO - Pharmacogenetics and Genomics
JF - Pharmacogenetics and Genomics
IS - 8
ER -