title: Effect of CYP3A5*3 on kidney transplant recipients treated with tacrolimus: a systematic review and meta-analysis of observational studies.
abstract: The highly variable pharmacokinetics of tacrolimus can hamper the optimal management of kidney transplant patients. This variability has been attributed to the genetic polymorphism of CYP3A5 6986A>G, but the evidence is not clear. We conducted a meta-analysis of studies evaluating the effect of CYP3A5 polymorphism on kidney transplant recipients with tacrolimus plasma concentration divided by daily dose per body weight (C/D) and clinical outcomes. We searched in MEDLINE and EMBASE. We found evidence suggesting a significantly lower C/D among CYP3A5*1 allele carriers compared with carriers of the CYP3A5*3/*3 genotype at weeks 1 and 2, and months 1, 3, 6 and 12. We demonstrated that the expresser genotype might have higher risk of acute rejection and chronic nephrotoxicity. In conclusion, CYP3A5 6986A>G polymorphism can affect tacrolimus pharmacokinetics and the incidence of acute rejection and chronic nephrotoxicity on kidney transplant recipients. Patients at high risk of developing tacrolimus-related complications could be detected even before their kidney transplant.
authors.affiliation: 1] Department of Internal Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile [2] Pharmacogenetic Unit, Drug Clinical Area, Hospital Universitari i Politècnic, La Fe and Instituto de Investigación Sanitaria La Fe, Valencia, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Rojas
authors.affiliation: 1] Department of Internal Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile [2] Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada.
authors.forename: I
authors.initials: I
authors.lastname: Neumann
authors.affiliation: Pharmacogenetic Unit, Drug Clinical Area, Hospital Universitari i Politècnic, La Fe and Instituto de Investigación Sanitaria La Fe, Valencia, Spain.
authors.forename: M José
authors.initials: MJ
authors.lastname: Herrero
authors.affiliation: Pharmacogenetic Unit, Drug Clinical Area, Hospital Universitari i Politècnic, La Fe and Instituto de Investigación Sanitaria La Fe, Valencia, Spain.
authors.forename: V
authors.initials: V
authors.lastname: Bosó
authors.affiliation: Pharmacogenetic Unit, Drug Clinical Area, Hospital Universitari i Politècnic, La Fe and Instituto de Investigación Sanitaria La Fe, Valencia, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Reig
authors.affiliation: Pharmacogenetic Unit, Drug Clinical Area, Hospital Universitari i Politècnic, La Fe and Instituto de Investigación Sanitaria La Fe, Valencia, Spain.
authors.forename: J Luis
authors.initials: JL
authors.lastname: Poveda
authors.affiliation: Pharmacogenetic Unit, Drug Clinical Area, Hospital Universitari i Politècnic, La Fe and Instituto de Investigación Sanitaria La Fe, Valencia, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Megías
authors.affiliation: Nephrology Department, Kidney transplant Unit, Hospital Universitari i Politècnic La Fe, Valencia, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Bea
authors.affiliation: 1] Pharmacogenetic Unit, Drug Clinical Area, Hospital Universitari i Politècnic, La Fe and Instituto de Investigación Sanitaria La Fe, Valencia, Spain [2] Clinical Pharmacology Unit, Drug Clinical Area, Hospital Universitari i Politècnic La Fe, Valencia, Spain [3] Department of Pharmacology, Faculty of Medicine, University of Valencia, Valencia, Spain.
authors.forename: S F
authors.initials: SF
authors.lastname: Aliño
mesh_terms: D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D006084:Graft Rejection / Q000175:diagnosis / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000009:adverse effects / Q000379:methods; D064887:Observational Studies as Topic / Q000379:methods; D016559:Tacrolimus / Q000627:therapeutic use*; D066027:Transplant Recipients
chemical_list: D007166:Immunosuppressive Agents; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; D016559:Tacrolimus