title: Effects of the CYP3A4*1B Genetic Polymorphism on the Pharmacokinetics of Tacrolimus in Adult Renal Transplant Recipients: A Meta-Analysis.
abstract: OBJECTIVE
  The association between the CYP3A4*1B single nucleotide polymorphism (SNP) and tacrolimus pharmacokinetics in different studies is controversial. Therefore, a meta-analysis was employed to evaluate the correlation between the CYP3A4*1B genetic polymorphism and tacrolimus pharmacokinetics at different post-transplantation times in adult renal transplant recipients.
  
  
  METHODS
  Studies evaluating the CYP3A4*1B genetic polymorphism and tacrolimus pharmacokinetics were retrieved through a systematical search of Embase, PubMed, the Cochrane Library, ClinicalTrials.gov and three Chinese literature databases (up to Sept. 2014). The pharmacokinetic parameters (weight-adjusted tacrolimus daily dose and tacrolimus trough concentration/weight-adjusted tacrolimus daily dose ratio) were extracted, and the meta-analysis was performed using Stata 12.1.
  
  
  RESULTS
  Seven studies (involving 1182 adult renal transplant recipients) were included in this meta-analysis. For the weight-adjusted tacrolimus daily dose, in all included renal transplant recipients (European & Indian populations), CYP3A4*1/*1 recipients required a significantly lower weight-adjusted tacrolimus daily dose than did CYP3A4*1B carriers at 7 days (WMD -0.048; 95% CI -0.083 ~ -0.014), 6 months (WMD -0.058; 95% CI -0.081 ~ -0.036) and 12 months (WMD - 0.061; 95% CI -0.096 ~ -0.027) post-transplantation. In light of the heterogeneity, the analysis was repeated after removing the only study in an Indian population, and CYP3A4*1/*1 European recipients (mostly Caucasian) required a lower weight-adjusted tacrolimus daily dose within the first year post-transplantation. The tacrolimus trough concentration/weight-adjusted tacrolimus daily dose ratio (C0/Dose ratio) was significantly higher in CYP3A4*1/*1 recipients than in CYP3A4*1B carriers at 6 months (WMD 52.588; 95% CI 22.387 ~ 82.789) and 12 months (WMD 62.219; 95% CI 14.218 ~ 110.221) post-transplantation. When the only study in an Indian population was removed to examine European recipients (mostly Caucasian), the significant difference persisted at 1 month, 6 months and 12 months post-transplantation.
  
  
  CONCLUSIONS
  Based on our meta-analysis, the CYP3A4*1B genetic polymorphism affects tacrolimus dose requirements and tacrolimus trough concentration/weight-adjusted tacrolimus daily dose ratio within the first year post-transplantation in adult renal transplant recipients, especially in European recipients (mostly Caucasian).
authors.affiliation: Department of Pharmacy, Peking University Third Hospital, Beijing, China.
authors.forename: Wei-Long
authors.initials: WL
authors.lastname: Shi
authors.affiliation: Department of Pharmacy, Peking University Third Hospital, Beijing, China.
authors.forename: Hui-Lin
authors.initials: HL
authors.lastname: Tang
authors.affiliation: Department of Pharmacy, Peking University Third Hospital, Beijing, China.
authors.forename: Suo-Di
authors.initials: SD
authors.lastname: Zhai
mesh_terms: D000328:Adult; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D006801:Humans; D016030:Kidney Transplantation; D020641:Polymorphism, Single Nucleotide; D016559:Tacrolimus / Q000493:pharmacokinetics* / Q000627:therapeutic use; D044465:White People
chemical_list: D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D016559:Tacrolimus