Chinese Journal of Tissue Engineering Research ›› 2012, Vol. 16 ›› Issue (18): 3255-3258.doi: 10.3969/j.issn.1673-8225.2012.18.006

Previous Articles     Next Articles

Effect of CYP3A5 genetic polymorphism on concentration and efficacy of tacrolimus in patients with kidney transplantation  

Li Xin-chang, Meng Dong-liang , Long Cheng-mei, Zeng Tao, Zeng Li-feng, Huang Yue-sheng   

  1. Department of Organ Transplantation, Jiangxi Provincial People’s Hospital, Nanchang  330006, Jiangxi Province, China
  • Received:2011-12-03 Revised:2012-02-27 Online:2012-04-29 Published:2012-04-29
  • About author:Li Xin-chang, Chief physician, Department of Organ Transplantation, Jiangxi Provincial People’s Hospital, Nanchang 330006, Jiangxi Province, China lixinchang863@163.com
  • Supported by:

    Key Projects of Social Development in Jiangxi Province*

PDF

441

Abstract:

BACKGROUND: There are reports relating to the relation between CYP3A5 genetype and tacrolimus concentration among European and American people in recent years, however, the data of the study available comes from the date after surgery within 1 month to 1 year and there lacks of early details.
OBJECTIVE: To study the relation between CYP3A5 genetic polymorphism and tacrolimus concentration per dose in kidney transplant recipients, and to evaluate the effect of CYP3A5 genotype on the acute rejection and the adverse effect of tacrolimus after kidney transplantation.
METHODS: Forty-five patients transplanted with planted cadaver kidney receiving the triple immunosuppressive (tacrolimus+mycophenolatemofetil+prednison), and the patients were divided into *1/*1 group (n=11), *1/*3 group (n=15), *3/*3 group (n=19) according to the CYP3A5 genotype. The initial dose of tacrolimus was 0.15 mg/kg per day and the dosage was adjusted according to the drug concentration to a target therapeutic window.
RESULTS AND CONCLUSION: At 7 day and 1 and 3 months after operation, the concentration per dosage in the *3/*3 group was significantly higher than that in the *1/*3 group and *1/*1 group (P < 0.05); the ratio of acute rejection in *1/*1 group was significantly higher than that in the *1/*3 group and *3/*3 group within 3 months (P < 0.05); the adverse effects of tacrolimus (nephrotoxicity, hyper glycosemia, neurotoxicity) were increased in CYP3A5 *3/*3 group compared with CYP3A5 *1/*1group within 3 months. The blood concentration of tacrolimus was lowest in *1/*1 genotype group within 3 months which induced the higher acute rejection rate, so the initial dosing regimen of tacrolimus was not the suitable for the treatment of early anti-rejection, and blood concentration of tacrolimus was highest in *3/*3 genotype group within 3 months which resulting in higher adverse effects. To choose the initial tacrolimus dosage required by individual patients according to the CYP3A5 genetic polymorphism is necessary for getting better outcome and reducing acute rejection in the CYP3A5 *1/*1 group and the adverse effect of tacrolimus in the CYP3A5 *3/*3 group, and which enhances the clinical effect of kidney transplantation.

CLC Number: