title: CYP3A5 *1 allele associated with tacrolimus trough concentrations but not subclinical acute rejection or chronic allograft nephropathy in Japanese renal transplant recipients.
abstract: OBJECTIVE
  We assessed reported associations of CYP3A5 *1 allele with a delay in achieving target tacrolimus concentrations, and occurrence of biopsy-confirmed subclinical acute rejection (SAR) and chronic allograft nephropathy (CAN) in Japanese subjects.
  
  
  METHODS
  Forty-one renal allograft recipients were studied. The targeted tacrolimus trough concentrations were 20-25 ng/mL up to 2 weeks post-transplantation, 10-15 ng/mL up to 6 weeks, and 5-10 ng/mL thereafter. At 1 month and 1 year post-transplantation, allograft biopsies were performed.
  
  
  RESULTS
  The CYP3A5 *1/*1 + *1/*3 (expresser) and *3/*3 (nonexpresser) alleles were detected in 19 and 22 patients, respectively. Although the mean trough concentrations were lower in CYP3A5 expressers than nonexpressers for the first 3 weeks, no difference in frequency of SAR among CYP3A5 genotypes was found. The mean trough concentrations were lower from 8 to 12 months post-transplantation, and the frequency of CAN was lower in CYP3A5 expressers.
  
  
  CONCLUSIONS
  In contrast to the previous reports, the CYP3A5 *1 allele was not associated with the frequency of SAR or CAN, suggesting that further studies of different immunosuppressive strategies using tacrolimus are needed to confirm the adequate dosing and concentration of tacrolimus for each CYP3A5 genotype.
authors.affiliation: Division of Renal Replacement Therapeutic Science, Department of Urology, Akita University School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan. shigerus@doc.med.akita-u.ac.jp
authors.forename: Shigeru
authors.initials: S
authors.lastname: Satoh
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Saito
authors.forename: Takamitsu
authors.initials: T
authors.lastname: Inoue
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kagaya
authors.forename: Masatomo
authors.initials: M
authors.lastname: Miura
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Inoue
authors.forename: Atsushi
authors.initials: A
authors.lastname: Komatsuda
authors.forename: Norihiko
authors.initials: N
authors.lastname: Tsuchiya
authors.forename: Toshio
authors.initials: T
authors.lastname: Suzuki
authors.forename: Tomonori
authors.initials: T
authors.lastname: Habuchi
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D044466:Asian People / Q000235:genetics; D051544:Cytochrome P-450 CYP3A / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006084:Graft Rejection / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000276:immunology*; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D016559:Tacrolimus / Q000008:administration & dosage / Q000276:immunology*; D014184:Transplantation, Homologous / Q000276:immunology; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; D016559:Tacrolimus