The Relationship Between CYP3A5 Gene Polymorphism To The Efficacy Of Tacrolimus In Renal Transplant Patients

Objective:To investigate the effects of CYP3A5,MDR1,SUMO4 and CYP3A4 gene polymorphisms on the efficacy of oral tacrolimus in renal transplant recipients.Methods: Forty patients were selected from 0 to 3 months after renal transplantation in the Second Affiliated Hospital of Nanhua University Of the patients,male or female,aged 18 years-55 years old.All patients were treated with FK506 + butcitrate + glucocorticoid triple immunosuppressive regimen.The whole blood concentration of tacrolimus was measured by automatic immunoassay system,and the ratio of concentration/dose was calculated.The DNAs of CYP3A5(rs776746),MDR1(rS1045642),SUMO4(rs237025)and CYP3A4(rs2242480)were amplified by PCR and sequenced.The effects of different genotypes of CYP3A5(rs776746),MDR1(r S1045642),SUMO4(rs237025)and CYP3A4(rs2242480)on the values of C/D of tacrolimus were studied.Results: The mean plasma concentration of tacrolimus and the C/D value was 176.5±90.5(ng/ml per mg/kg)for one week,two weeks,one month,two months after surgery in 40 renal transplant recipients.CYP3A5 gene loci(rs776746)different genotypes of early postoperative tacrolimus C/D value was significantly different(P<0.05),CYP3A5 homozygous mutant CC type of tacrolimus after C/D value is higher.MDR1(rs1045642)gene loci of different genotypes of early postoperative tacrolimus C/D value difference was significantly different(P<0.05),MDR1 mutant homozygous TT postoperative tacrolimus blood concentrations is higher.There was no statistical significance among SUMO4(rs237025)genetic locus for the C/D value of the early postoperative period(P>0.05).There was no statistical significance among CYP3A4(rs2242480)genetic locus for the C/D value of the gene at the early stage of the operation(P>0.05).Conclusion: 1.CYP3A5(rs776746),MDR1(rs1045642)gene polymorphism had an effect on the early oral administration of tacrolimus C/D in patients with renal transplantation.rs77674646 mutant homozygous CC patients were able to reach the target blood drug concentration by taking a lower dose than the wild homozygous TT patients.The rs1045642 patients with homozygous homozygous CC(rs1045642)were more likely to reach the target blood drug concentration than those with a mutated homozygous type.2.There was no significant difference between the polymorphism of SUMO4(rs237025)and CYP3A4(rs2242480)gene in the C/D values of oral tacrolimus in patients with renal transplantation.