title: Meta-analysis and systematic review of the effect of the donor and recipient CYP3A5 6986A>G genotype on tacrolimus dose requirements in liver transplantation.
abstract: OBJECTIVE
  A meta-analysis was carried out of published studies on the effect of the CYP3A5 6986A>G polymorphism in liver donors and transplant recipients on tacrolimus pharmacokinetics.
  
  
  METHODS
  Cohort studies that evaluated the relationship between the CYP3A5 polymorphism in liver donors and transplant recipients and tacrolimus, trough blood concentration normalized for the daily dose (C) per kilogram body weight (D) (C/D, ng/ml/mg/kg/day) up to 1 year after transplantation, were included. Data were not restricted by patient age or the language or journal of publication. A literature search was conducted using the Cochrane Library, MEDLINE, EMBASE, and grey literature, and articles published up to 24 April 2013 were selected. Data were pooled (random-effects model), and the results were expressed as the mean difference of the corresponding C/D ratios and 95% confidence intervals.
  
  
  RESULTS
  Six studies involving donor genotypes (254 patients) and four involving recipient genotypes (180 patients) were ultimately included. The meta-analysis showed the C/D ratio to be significantly higher in recipients with nonexpresser donor variants at all time points. In recipients, the variant did not influence the C/D ratio.
  
  
  CONCLUSIONS
  The presence of the CYP3A5 6986A>G polymorphism in the donor affects tacrolimus pharmacokinetics in the recipient, although only the evidence available for the first month after transplantation was of adequate quality for demonstrating a significant difference. The evidence provided here shows no effect of the recipient genotype; however, the quality of the evidence was low, thereby precluding the drawing of firm conclusions.
authors.affiliation: aDepartment of Internal Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile bPharmacogenetic Unit, Drugs Clinical Area, Hospital Universitari i Politècnic La Fe e Instituto de Investigación Sanitaria La Fe. cHepatology Unit. Hospital Universitari i Politècnic La Fe dClinical Pharmacology Unit, Drugs Clinical Area, Hospital Universitari i Politècnic La Fe eDepartment of Pharmacology, Faculty of Medicine, Universitat de Valencia fCenter for Public Health Research-Valencia (CSISP-FISABIO), Health Services Research Network in Chronic Diseases (RESISSEC), Valencia, Spain.
authors.forename: Luis E
authors.initials: LE
authors.lastname: Rojas
authors.forename: María J
authors.initials: MJ
authors.lastname: Herrero
authors.forename: Virginia
authors.initials: V
authors.lastname: Bosó
authors.forename: María
authors.initials: M
authors.lastname: García-Eliz
authors.forename: José L
authors.initials: JL
authors.lastname: Poveda
authors.forename: Julian
authors.initials: J
authors.lastname: Librero
authors.forename: Salvador F
authors.initials: SF
authors.lastname: Aliño
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016031:Liver Transplantation; D019520:Living Donors; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D016559:Tacrolimus / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014180:Transplantation; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; D016559:Tacrolimus