title: Association of CYP3A polymorphisms with the pharmacokinetics of cyclosporine A in early post-renal transplant recipients in China.
abstract: OBJECTIVE
  To evaluate retrospectively the association of cytochrome P450 3A (CYP3A) and ATP-binding cassette sub-family B member 1 (ABCB1) gene polymorphisms with the pharmacokinetics of cyclosporine A (CsA) in Chinese renal transplant patients.
  
  
  METHODS
  One hundred and twenty-six renal transplant patients were recruited. Blood samples were collected, and corresponding clinical indices were recorded on the seventh day after the procedure. The patients were genotyped for CYP3A4*1G, CYP3A5*3C, ABCB1 1236 C>T, ABCB1 2677 G>T/A, and ABCB1 3435 C>T polymorphisms. Whole blood trough concentrations of CsA at time zero (C(0)) were measured before the drug administration. A multiple regression model was developed to analyze the effects of genetic factors on the CsA dose-adjusted C(0) (C(0)/dose) based on several clinical indices.
  
  
  RESULTS
  The CYP3A5*3C polymorphism influenced the C(0) and C(0)/dose of CsA, which were significantly higher in patients with the GG genotype than in patients with the AA or GA genotypes. No significant differences were detected for other SNPs (CYP3A4*1G, ABCB1 1236 C>T, ABCB1 2677 G>T/A, and ABCB1 3435 C>T). In a univariate analysis using Pearson's correlation test, age, hemoglobin, blood urea nitrogen and blood creatinine levels were significantly correlated with the log-transformed CsA C(0)/dose. In the multiple regression model, CYP3A5*3C, age, hemoglobin and blood creatinine level were associated with the log-transformed CsA C(0)/dose.
  
  
  CONCLUSIONS
  CYP3A5*3C correlates with the C(0)/dose of CsA on the seventh day after renal transplantation. The allele is a putative indicator for the optimal CsA dosage in the early phase of renal transplantation in the Chinese population.
authors.affiliation: Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha 410078, China.
authors.forename: Xiang-guang
authors.initials: XG
authors.lastname: Meng
authors.forename: Cheng-xian
authors.initials: CX
authors.lastname: Guo
authors.forename: Guo-qing
authors.initials: GQ
authors.lastname: Feng
authors.forename: Ying-chun
authors.initials: YC
authors.lastname: Zhao
authors.forename: Bo-Ting
authors.initials: BT
authors.lastname: Zhou
authors.forename: Jian-le
authors.initials: JL
authors.lastname: Han
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.forename: Yong
authors.initials: Y
authors.lastname: Shi
authors.forename: Hong-yao
authors.initials: HY
authors.lastname: Shi
authors.forename: Ji-ye
authors.initials: JY
authors.lastname: Yin
authors.forename: Xiang-dong
authors.initials: XD
authors.lastname: Peng
authors.forename: Qi
authors.initials: Q
authors.lastname: Pei
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Guo
authors.initials: G
authors.lastname: Wang
authors.forename: Meng
authors.initials: M
authors.lastname: He
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.forename: Jing-ke
authors.initials: JK
authors.lastname: Yang
authors.forename: Hong-hao
authors.initials: HH
authors.lastname: Zhou
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000235:genetics*; D002681:China; D016572:Cyclosporine / Q000097:blood / Q000493:pharmacokinetics*; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D005260:Female; D006239:Haplotypes; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000493:pharmacokinetics*; D016030:Kidney Transplantation; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D055815:Young Adult
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; D016572:Cyclosporine; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A