Association Of Gene Polymorphisms In Renal Transplant Recipients With Myelosuppression And The Influence Of Gene Polymorphism Of Wuzhi Capsules On Increasing Tacrolimus Concentration

OBJECTIVE To explore the correlation between gene polymorphisms in renal transplant recipients and Myelosuppression after renal transplantation,and the effect of genetic polymorphism on the concentration of Tacrolimus in combination with Wuzhi capsules for clinical Tacrolimus individualization Provide reference for medication.METHODS 1.CYP3A4,CYP3A5,CYP2C19,MDR1,PXR,POR,PPAR,IL-3,IL-10,CTLA4 genotyping were performed using Sequenom MassArray system.The adverse reactions during 369 renal transplant recipients were recorded by follow-up observation.Statistical software and Haploview 4.2 genetic analysis software were used to study the association of genetic polymorphisms with adverse reactions during drug use.2.To analyze and compare the relationship between the gene polymorphism of TAC group and the drug concentration;to analyze and compare the effects of different genotypes on the concentration of TAC in the TAC combined with Wuzhi capsules group.RESULTS 1.Of the 369 enrolled patients,265 developed myelosuppression after kidney transplantation.These patients recovered or remained stable after dose reduction or suspension of medication or symptomatic treatment.2.To analyze the effect of different genotypes on myelosuppression after renal transplantation: CYP3A4(rs4646437)gene polymorphism was associated with bone marrow suppression after renal transplantation,CYP3A4(rs464643AA/AG/GG)genotypes in normal group and myelosuppression group The distribution was different,p<0.05.3.There were 194 renal transplant recipients in the monotherapy group and the combination group,and the distribution of each genotype was in line with Hardy-Weinberg equilibrium(P>0.05).The factors influencing C/D of tacromycin were whether combined use of wuzhi capsule and genotype of CYP3A5(rs776746)(P<0.05).In patients with CYP3A5(rs776746)AA,there was no statistically significant difference in the C/D of tacrolimus between the combined group and the single group(P>0.05),while there was a statistically significant difference in the C/D of tacrolimus between the two groups with other genotypes(P<0.05).CONCLUSION 1.The genetic polymorphism of CYP3A4(rs4646437)was associated with myelosuppression after renal transplantation.Among them,CYP3A4(rs4646437AA)had the lowest incidence of myelosuppression,followed by AG,and GG had the highest myelosuppression.2.Wuzhi capsules and CYP3A5(rs776746)gene polymorphism had an effect on oral tacrolimus C/D values in renal transplant recipients.Wuzhi capsule could significantly increase the C/D value of tacrolimus in patients with CYP3A5*3 GG and GA,but not on patients with CYP3A5*3 AA.