Effects of CYP3A5 * 3 polymorphisms on tacrolimus pharmacokinetic in renal transplantation recipients by PyrosequencingTM
10.3760/cma.j.issn.0254-1785.2010.05.007
- VernacularTitle:肾移植受者CYP3A5基因多态性对术后他克莫司药物代谢的影响
- Author:
Dingyun LI
;
Zhi LI
;
Lijun ZHU
;
Qifa YE
;
Bing DU
;
Guo WANG
;
Yingzi MING
;
Ke CHENG
;
Xingguo SE
;
Honghao ZHOU
- Publication Type:Journal Article
- Keywords:
Kidney transplantation;
Tacrolimus;
Cytochrome P-450 CYP3AS;
Pyrosequencing TM
- From:
Chinese Journal of Organ Transplantation
2010;31(5):280-283
- CountryChina
- Language:Chinese
-
Abstract:
Objective To study the influence of CYP3A5 genetic polymorphism on tacrolimus metabolism in renal transplantation recipients and evaluate the methods of detecting CYP3A5* 3 polymorphism. Methods Ninety-seven renal recipients receiving the triple immunosuppressive (tacrolimus + mycophenolate mofetil + prednison) were genotyped for CYP3A5* 3 polymorphisms by the Pyrosequencing TM assays. Tacrolimus trough concentration of the patients was measured by enzyme multiplied immunoassay technique, and concentration/adjusted dose ratio (C/D) was investigated at the 7th day, 14th day, 1st month, 3rd month and 6th month after renal transplantation. Results The Pyrosequencing TM assays allowed for quick and accurate detection of CYP3A5* 3 genotypes. There were CYP3A5* 1/* 1 genotype in 17 cases (17. 5%), * 1/* 3 in 35cases (36. 1 %) and *3/* 3 in 45 cases (46.4 %) identified in 97 renal recipients. The C/D of CYP3A5 * 1/* 1 and * 1/* 3 patients was significantly lower than that of * 3/* 3 patients (P<0. 01)after renal transplantation. Conclusion The CYP3A5* 3 polymorphisms are significantly correlated with tacrolimus pharmacokinetic in renal transplant recipients. Detecting the CYP3AS* 3 genotype of the recipient before the transplantation by the Pyrosequencing TM assays can be used to help determine the optimal initial dosage after transplantation, resulting in individualized drug therapy.