title: Reduced variability of tacrolimus trough level in once-daily tacrolimus-based Taiwanese kidney transplant recipients with high-expressive genotype of cytochrome P450 3A5.
abstract: BACKGROUND
  Our previous study results indicated that conversion from twice-daily Prograf to once-daily Advagraf associated with lower variability of tacrolimus blood trough level. Some factors, such as frequency of interaction by food exposure, expression of cytochrome P450 3A5 genetic polymorphism, and other interactions of unknown factors, could be the reasons for the change of variability. We aimed to clarify the impact of cytochrome P450 3A5 genetic polymorphism on the variability of tacrolimus blood trough level in Taiwanese kidney transplant recipients.
  
  
  METHODS
  We collected blood samples from kidney transplant recipients to prepare DNA and then performed single-nucleotide polymorphism genotyping by using the restriction fragment length polymorphism.
  
  
  RESULTS
  We found that 79 (52.7%) of 150 kidney transplant recipients had the low-expressive genotype (CYP3A5*3/*3), whereas the other 71 (47.3%) kidney transplant recipients had high-expressive genotype (CYP3A5*1/*1 and CYP3A5*1/*3). The prevalence of high-expressive genotype is higher than previous reports from western countries. Compared with the patients with high-expressive genotype, the average dose-normalized trough level of tacrolimus was significantly higher in patients with low-expressive genotype. Interestingly, when patients converted from twice-daily Prograf to once-daily Advagraf, the percent coefficient of variation of tacrolimus trough level was significantly decreased in patients with high-expressive genotype.
  
  
  CONCLUSIONS
  This study suggested that there is a potential benefit for kidney transplant recipients with cytochrome P450 3A5 high-expressive genotype (*1/*1 or *1/*3) to convert from Prograf to once-daily Advagraf.
authors.affiliation: Division of Nephrology, Taichung Veterans General Hospital; School of Medicine, Chung Shan Medical University, Taiwan; Graduate Institute of Clinical Medical Science, School of Medicine, China Medical University, Taiwan; Institute of Biomedical Science, National Chung Hsing University, Taiwan; Department of Life Science, Tunghai University, Taiwan. Electronic address: wmj530@gmail.com.
authors.forename: M-J
authors.initials: MJ
authors.lastname: Wu
authors.affiliation: Institute of Clinical Medicine, School of Medicine, National Yang Ming University, Taiwan.
authors.forename: C-H
authors.initials: CH
authors.lastname: Chang
authors.affiliation: Department of Pharmacy, Taichung Veterans General Hospital.
authors.forename: C-Y
authors.initials: CY
authors.lastname: Cheng
authors.affiliation: Division of Nephrology, Taichung Veterans General Hospital; School of Medicine, Chung Shan Medical University, Taiwan.
authors.forename: K-H
authors.initials: KH
authors.lastname: Shu
authors.affiliation: Division of Nephrology, Taichung Veterans General Hospital; Graduate Institute of Clinical Medical Science, School of Medicine, China Medical University, Taiwan.
authors.forename: C-H
authors.initials: CH
authors.lastname: Chen
authors.affiliation: Division of Nephrology, Taichung Veterans General Hospital; School of Medicine, Chung Shan Medical University, Taiwan.
authors.forename: C-H
authors.initials: CH
authors.lastname: Cheng
authors.affiliation: Division of Nephrology, Taichung Veterans General Hospital; Graduate Institute of Clinical Medical Science, School of Medicine, China Medical University, Taiwan.
authors.forename: T-M
authors.initials: TM
authors.lastname: Yu
authors.affiliation: Division of Nephrology, Taichung Veterans General Hospital; Graduate Institute of Clinical Medical Science, School of Medicine, China Medical University, Taiwan.
authors.forename: Y-W
authors.initials: YW
authors.lastname: Chuang
authors.affiliation: Division of Nephrology, Taichung Veterans General Hospital; Graduate Institute of Clinical Medical Science, School of Medicine, China Medical University, Taiwan.
authors.forename: S-T
authors.initials: ST
authors.lastname: Huang
authors.affiliation: Division of Nephrology, Taichung Veterans General Hospital; Department of Life Science, Tunghai University, Taiwan.
authors.forename: S-F
authors.initials: SF
authors.lastname: Tsai
authors.affiliation: Division of Urology, Taichung Veterans General Hospital.
authors.forename: H-C
authors.initials: HC
authors.lastname: Ho
authors.affiliation: Division of Urology, Taichung Veterans General Hospital.
authors.forename: J-R
authors.initials: JR
authors.lastname: Li
authors.affiliation: Yumin Medical Corporation Yumin Hospital, Taiwan.
authors.forename: Y-N
authors.initials: YN
authors.lastname: Shiu
authors.affiliation: Department of Pediatrics, Taichung Veterans General Hospital; Institute of Clinical Medicine, School of Medicine, National Yang Ming University, Taiwan.
authors.forename: Y-C
authors.initials: YC
authors.lastname: Fu
mesh_terms: D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D016030:Kidney Transplantation; D016559:Tacrolimus / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D013624:Taiwan
chemical_list: D007166:Immunosuppressive Agents; D051544:Cytochrome P-450 CYP3A; D016559:Tacrolimus