title: Polymorphisms in CYP3A5*3 and MDR1, and haplotype modulate response to plasma levels of tacrolimus in Chinese renal transplant patients.
abstract: BACKGROUND
  The purpose of this study was to investigate the effects of polymorphisms in CYP3A5*3, CYP3AP1, and MDR1, and of haplotype, on plasma levels of tacrolimus in Chinese patients after renal transplantation, and to assess the relationship between polymorphisms and the variability of concentration/dose of tacrolimus for optimization and individualization regimens.
  
  
  METHODS
  The MALDI-TOF method was used to detect the genotype of CYP3A5*3, CYP3AP1, and MDR-1 in kidney transplant recipients (n=63) receiving tacrolimus. Patients were assigned to 3 groups according to genotype. Peripheral blood was collected and the serum concentrations of tacrolimus were determined by EMIT 2000 after 12 hours of administration. Dose-adjusted concentrations of tacrolimus were calculated according to the different groups.
  
  
  RESULTS
  We found that tacrolimus dose-adjusted C0 was larger in CYP3A5*3 and CYP3AP1 non-expressing renal transplant patients than in those who expressed the genes. In addition, wild-type homozygotes for MDR1 C3435T had a slightly lower dose-adjusted C0 compared with heterozygotes. However, no evidence was found that there was relationship between the MDR1 1236CT, 2677GT or haplotype polymorphisms and tacrolimus pharmacokinetics.
  
  
  CONCLUSIONS
  The CYP3A5 genotype shows the most important association with tacrolimus concentrations. Our study suggests that a pharmacogenetic approach could be employed to predict individual drug availability differences in future.
authors: Department of Pharmacology, 3rd Affiliated Hospital, Soochow University, Jiangsu Changzhou, China.
authors: Ping
authors: P
authors: Wu
authors: Xuefeng
authors: X
authors: Ni
authors: Mingli
authors: M
authors: Wang
authors: Xianlin
authors: X
authors: Xu
authors: Guanghua
authors: G
authors: Luo
authors: Yan
authors: Y
authors: Jiang
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D002681:China; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D017931:DNA Primers / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D006239:Haplotypes; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D016030:Kidney Transplantation / Q000502:physiology*; D015810:Linkage Disequilibrium; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D016559:Tacrolimus / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D017931:DNA Primers; D007166:Immunosuppressive Agents; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; D016559:Tacrolimus