title: The effect of ABCB1 C3435T polymorphism on pharmacokinetics of tacrolimus in liver transplantation: a meta-analysis.
abstract: OBJECTIVE
  The effect of ABCB1 C3435T SNP on the pharmacokinetics of immunosuppressive drug tacrolimus in different studies was conflicting. So a meta-analysis was employed to study the correlation of ABCB1 C3435T SNP and the pharmacokinetics of tacrolimus at different post-transplantation times.
  
  
  METHODS
  Several studies about ABCB1 C3435T polymorphism and the pharmacokinetics of tacrolimus were collected through the search on PubMed and the Cochrane Library. After the extraction of pharmacokinetic parameters from these studies, a meta-analysis was performed on the software STATA version 11.0.
  
  
  RESULTS
  A total of 9 studies were adopted including 558 liver transplant recipients. For the dose of tacrolimus, the subjects with wild-type CC had a significantly higher tacrolimus dose than homozygous mutated genotype TT within 1 week (WMD=0.01 (0.00, 0.02), P=0.014) and the similar result in recipients with heterozygous CT compared with TT after transplantation for 1 month (WMD=0.01 (0.00, 0.02), P=0.002). For the tacrolimus concentration/dose ratio, subjects with CT had higher C/D ratio than those with CC and TT at different post-transplantation times. A subgroup analysis based on different ethnic populations was also carried out. Donors' genotypes were also considered in this meta-analysis.
  
  
  CONCLUSIONS
  Through this meta-analysis for the including studies about the pharmacokinetics of tacrolimus and ABCB1 C3435T SNP, several significant associations were obtained. Particularly, the Caucasians showed more significant associations between the C/D ratio and ABCB1 C3435T polymorphism; however, the correlations were not steady at different post-transplantation times.
authors.affiliation: Department of Health Statistics, School of Public Health, Tianjin Medical University, 22 Qi-Xiang-Tai Road, Heping District, Tianjin 300070, China.
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Liu
authors.forename: Changping
authors.initials: C
authors.lastname: Li
authors.forename: Zhuang
authors.initials: Z
authors.lastname: Cui
authors.forename: Xiaomeng
authors.initials: X
authors.lastname: Fu
authors.forename: Shu
authors.initials: S
authors.lastname: Zhang
authors.forename: Lin-Lin
authors.initials: LL
authors.lastname: Fan
authors.forename: Jun
authors.initials: J
authors.lastname: Ma
authors.forename: Guang
authors.initials: G
authors.lastname: Li
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics*; D017093:Liver Failure / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D016031:Liver Transplantation; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000502:physiology; D011379:Prognosis; D016559:Tacrolimus / Q000493:pharmacokinetics*; D019172:Transplantation Conditioning / Q000379:methods
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D007166:Immunosuppressive Agents; D016559:Tacrolimus
keywords: ABCB1 C3435T; Association; CI; Meta-analysis; P-glycoprotein; P-gp; Polymorphism; SNPs; Tacrolimus pharmacokinetics; WMD; confidence intervals; single nucleotide polymorphisms; weighted mean differences