Effect of cytochrome P450 3A5 (CYP3A5) genotype on tacrolimus dose requirement in renal transplant patients
10.3760/cma.j.issn.0254-1785.2014.01.007
- VernacularTitle:细胞色素P450 3A5基因分型对肾移植受者他克莫司剂量的影响
- Author:
Shi FENG
;
Xian YANG
;
Hongfeng HUANG
;
Jianyong WU
;
Rending WANG
;
Jianghua CHEN
- Publication Type:Journal Article
- Keywords:
Cytochrome P450;
Tacrolimus;
Kidney transplantation.
- From:
Chinese Journal of Organ Transplantation
2014;35(1):25-28
- CountryChina
- Language:Chinese
-
Abstract:
Objective To study the effects of CYP3A5 * 1 and CYP3A5 * 3 genotypes on tacrolimus dose requirement.Method We tested archival peripheral blood of 69 kidney recipients for CYP3A5 genotyping by polymerase chain reaction.The dose,blood concentrations and dose-normalized blood concentrations of tacrolimus were measured at 1st and 2nd month after the renal transplantation.Result There were 6 cases of CYP3A5 * 1/* 1 (8.7%),22 cases of CYP3A5 * 1/* 3 (31.9%),and 41 cases of CYP3A5 * 3/* 3 (59.4%).At 1st and 2nd month after the renal transplantation,the carriers of CYP3A5 * 1 genotype had a higher mean tacrolimus dose than CYP3A5 * 3/* 3 genotye (both P<0.000 1),and those of CYP3A5 * 1 genotype had lower mean tacrolimus concentrations than CYP3A5 * 3/* 3 genotye (P=0.020 8,and P =0.019 1 respectively).Meanwhile,the carriers of CYP3A5 * 1 genotype had lower dose-normalized blood concentrations of tacrolimus than CYP3A5 * 3/* 3 genotye (P<0.000 1) at 1st month after the renal transplantation,as well as at 2nd month after the renal transplantation (P =0.0191).Hepatic and renal function showed no significant effect on tacrolimus dose adjusted concentration at 1st and 2nd month after transplantation.Gender did not show a significant impact on tacrolimus dose.Conclusion CYP3A5 * 1 carriers needhigher tacrolimus dose than CYP3A5 * 3 homozygote to achieve the target blood concentration.CYP3A5 genotyping is a new approach for detecting tacrolimus dose requirement in kidney recipients.