title: CYP3A4 genetic polymorphisms predict cyclosporine-related clinical events in Chinese renal transplant recipients.
abstract: BACKGROUND
  Cyclosporin A (CsA) is a substrate of both cytochrome P450 3A (CYP3A) and P-glycoprotein (P-gp), some of the single nucleotide polymorphisms (SNPs) in these genes are associated with interindividual variations in CsA pharmacokinetics. We studied the influence of these SNPs on the incidence of rejection and CsA nephrotoxicity, as well as pneumonia within one year after renal transplant and post-transplantation diabetes mellitus (PTDM), in order to find whether genetic evaluation may help to identify patients at risk and to modulate CsA therapy to optimize graft and patient outcomes.
  
  
  METHODS
  A total of 208 renal transplant recipients receiving CsA were genotyped for ABCB1 (C1236T, G2677T/A, and C3435T), CYP3A4 1G, and CYP3A5 3 by direct sequencing method. Retrospective case control study was utilized to identify the association between CYP3A4 1G, CYP3A5 3, ABCB1 genetic polymorphisms and CsA-related outcomes.
  
  
  RESULTS
  The patients with a CYP3A4 1G/ 1G genotype were found to have a higher incidence of acute rejection compared with those with CYP3A4 1/1.
  
  
  CONCLUSIONS
  CYP3A4 1G/1G genotype predict increased risk of acute rejection, so genetic evaluation may partly help to identify patients at risk and to modulate CsA therapy to optimize graft and patient outcomes.
authors.affiliation: Department of Nephrology, Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Yu-Yuan
authors.initials: YY
authors.lastname: Wang
authors.forename: Ming
authors.initials: M
authors.lastname: Zhang
authors.forename: Fu-Ming
authors.initials: FM
authors.lastname: Lu
authors.forename: Zheng
authors.initials: Z
authors.lastname: Jiao
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Qiu
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; D016022:Case-Control Studies; D016572:Cyclosporine / Q000009:adverse effects* / Q000627:therapeutic use; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D016030:Kidney Transplantation; D011110:Polymorphism, Genetic / Q000235:genetics*; D012189:Retrospective Studies
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; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human