CYP3A5 *1 allele associated with tacrolimus trough concentrations but not subclinical acute rejection or chronic allograft nephropathy in Japanese renal transplant recipients.
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.
Satoh
Shigeru
S
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
Saito
Mitsuru
M
Inoue
Takamitsu
T
Kagaya
Hideaki
H
Miura
Masatomo
M
Inoue
Kazuyuki
K
Komatsuda
Atsushi
A
Tsuchiya
Norihiko
N
Suzuki
Toshio
T
Habuchi
Tomonori
T
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
D007166:Immunosuppressive Agents; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; D016559:Tacrolimus