The effect of CYP3A5 6986A>G and ABCB1 3435C>T on tacrolimus dose-adjusted trough levels and acute rejection rates in renal transplant patients:  a systematic review and meta-analysis.
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 CYP3A53/3 compared with CYP3A51 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.
Department of Pharmaceutical Sciences and Interdepartmental Research Center of Pharmacology and Pharmacogenomics-CRIFF, Università del Piemonte Orientale 'A. Avogadro', Novara, Italy.
Salvatore
S
Terrazzino
Marco
M
Quaglia
Piero
P
Stratta
Pier L
PL
Canonico
Armando A
AA
Genazzani
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000483:Alleles; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D056726:Genetic Association Studies; D005838:Genotype; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D016030:Kidney Transplantation / Q000276:immunology; D015996:Survival Rate; D016559:Tacrolimus / Q000008:administration & dosage*
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D007166:Immunosuppressive Agents; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; D016559:Tacrolimus