title: Interactive effects of CYP3A4, CYP3A5, MDR1 and NR1I2 polymorphisms on tracrolimus trough concentrations in early postrenal transplant recipients.
abstract: OBJECTIVE
  To evaluate the influences of CYP3A4, CYP3A5, MDR1 and NR1I2 polymorphisms on tacrolimus concentration in early postrenal transplant recipients.
  
  
  METHODS
  A total of 159 patients were included, dose-adjusted tacrolimus trough concentration on day 7 after transplantation (C0D7/D) was calculated and 10 SNPs in four genes were genotyped.
  
  
  RESULTS
  CYP3A5*3 explained 32.8% of variability of tacrolimus C0D7/D. CYP3A4*1G, MDR1 1236-2677-3435 diplotype and NR1I2 -25385C > T explained 21.4% of variability of tacrolimus C0D7/D in CYP3A5 nonexpressers.
  
  
  CONCLUSIONS
  CYP3A5*3 was the predominant determinant affecting tacrolimus concentration. Genotyping of CYP3A4/MDR1/NR1I2 polymorphisms may be helpful for better guiding tacrolimus dosing in CYP3A5 nonexpressers.
authors.affiliation: Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, 132 Waihuan Dong Road, University City, Guangzhou 510006, China.
authors.forename: Jia-li
authors.initials: JL
authors.lastname: Li
authors.affiliation: Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, 132 Waihuan Dong Road, University City, Guangzhou 510006, China.|Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Dong Road, Guangzhou 510060, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Liu
authors.affiliation: Kidney Transplant Department, Transplant Center, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan Road II, Guangzhou 510080, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Fu
authors.affiliation: Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, 132 Waihuan Dong Road, University City, Guangzhou 510006, China.|School of Pharmaceutical Sciences, Guangzhou Medical University, Xinzao, Panyu District, Guangzhou 510182, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, 132 Waihuan Dong Road, University City, Guangzhou 510006, China.
authors.forename: Xue-ding
authors.initials: XD
authors.lastname: Wang
authors.affiliation: Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, 132 Waihuan Dong Road, University City, Guangzhou 510006, China.
authors.forename: Xiao-man
authors.initials: XM
authors.lastname: Liu
authors.affiliation: Kidney Transplant Department, Transplant Center, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan Road II, Guangzhou 510080, China.
authors.forename: Long-shan
authors.initials: LS
authors.lastname: Liu
authors.affiliation: Kidney Transplant Department, Transplant Center, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan Road II, Guangzhou 510080, China.
authors.forename: Chang-xi
authors.initials: CX
authors.lastname: Wang
authors.affiliation: Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, 132 Waihuan Dong Road, University City, Guangzhou 510006, China.
authors.forename: Min
authors.initials: M
authors.lastname: Huang
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000379:methods; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid / Q000235:genetics*; D016559:Tacrolimus / Q000627:therapeutic use*; D066027:Transplant Recipients; D055815:Young Adult
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D007166:Immunosuppressive Agents; C000625852:NR1I2 protein, human; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D016559:Tacrolimus
keywords: CYP3A4; CYP3A5; MDR1; NR1I2; pharmacogenetics; renal transplant; tacrolimus