Intergrated analysis of CYP3A5 and ABCB1 gene polymorphisms in renal transplanted recipients treated by Tacrolimus / 中华器官移植杂志

ABSTRACT

Objective To approach the effect of CYP3A5 6986A＞G (rs776746) and ABCB1 3435C＞T (rs104564) on plasma tacrolimus(FK506) dose adjusted blood trough concentrations(C0/D) in kidney transplanted patients.Method Totally 125 renal transplanted recipients were recruited,and gene sequencing method were used to detect the genotype of CYP3A5 6986A＞G and ABCB1 3435C＞ T.FK506 trough concentration of 125 patients was detected by enzyme multiplies immunoassay technique (EMIT) after the surgery over 6 month.The relevance between the ratio of trough concentration/dosage and polymorphisms was analyzed.Result In 125 renal transplanted receipients,the allele frequency of CYP3A5 and ABCB1 genetic variants was 74％ and 34.8％,respectively.After 6 months,the C0/D ration in the homozygous mutant CYP3A5 * 3/* 3 receiptients was significant higher than that in the homozygous wild type * 1/* 3 and heterozygous mutant * 1/* 1 receiptients (P ＜ 0.05).And there was no significant difference of the Co/D ration between CYP3A5 * 1/* 1 and CYP3A5 * 1/* 3 receipients(P＞0.05).The the C0/D ration in homozygous wild type ABCB1 T/T and homozygous mutant T/C receipients was significant higher than that in heterozygous mutant C/C receipients (P＜0.05),and there was no significant difference of the C0/D ration between T/C and T/T receipients (P＞ 0.05).Conclusion The study shows that the the polymorphism of CYP3A5 and ABCB1 genes was significantly correlated with the trough C0/D value of the recipients after renal transplantation who were treated by Tacrolimus for more than half a year.The detection of the SNP of the CYP3A5 and ABCB1 will be useful for FK506 dosage adjustment.