To Explore The Value Of Polymorphisms Of Immunosuppressor In The Individual Therapy Plan For Renal Transplantation Patients

Objective:We investigated IMPDH and CYP3A5 gene polymorphisms involved in MPA response and CNI trough concentrations. At the same time we detected MPA and CNI concentration. We study the gene polymorphisms association with immunosuppressor concentration and clinical effect to provide the basis of individual therapy.Methods:We genotyped the single nucleotide polymorphisms of IMPDH and CYP3A5 by using derect sequencing SNPs Genotyping Assays. And we made the dynamic follow up after transplantation. The patients were assigned into three genotype groups according to their CYP3A5 allele *3/*3, *1/*3, or *1/*1. We detect the trough concentrations of the Cs A and Tac which were detected by fluorescence polarization immunoassay and microparticle enzyme immunoassay in every follow-up point. In addition, the association of SNPs with 1-year post-transplantat acute rejection was analyzed.Then we monitored the AUC of MPA after transplantation to explore the clinical value.Result:Of the 105 patients, the number of patients in Tac and Cs A group was 64 and 41, respectively. During the first month after transplantation, recipients with CYP3A5*3/*3 allele exhibited significantly higher Tac C0 than the recipients with CYP3A5*1/*1 allele. The Tac dose/day used for recipients with CYP3A5*3/*3 allele was significantly lower than that for recipients with CYP3A5*1/*1 or CYP3A5*1/*3 allele. During the 4-year follow-up, the Tac C0 of recipients with CYP3A5*3/*3 allele was significantly higher than that of the recipients with CYP3A5*1/*3 and CYP3A5*1/*1 allele. The trough concentrations/doses of Cs A were not associated with the CYP3A5 SNPs.Of the 105 patients, 35(33.33%) patients presented with IMPDH1rs2278293 GG genotype, 49(46.67%) patients presented with GA and 21(20.00%) patients presented with AA. 22(20.95%) patients presented with IMPDH1rs2278294 GG genotype, 49(46.67%) patients presented with GA and 34(32.38%) patients presented with AA.14(13.33%) patients presented with IMPDH2rs11706052 GA genotype and 91(86.67%) patients presented with AA. In the whole group of 105 patients, the IMPDH1 rs2278293, rs2278294 were associated with acute rejection over the first year post-transplant. Combined rs2278293 and rs2278294 genotype was associated with acute rejection after one year post-transplant. The AUC in 13 of 49 patients was less than 30 mg.h/L. The low-AUC group had higher rate of acute rejection.Conclusions:(1) Patients with homozygous CYP3A5*3/*3 allele need less dosage of Tac to maintain a therapeutic concentration after renal transplantation.(2) IMPDH1 rs2278293, rs2278294 SNP were associated with a lower risk of acute rejection and may improve MPA treatment outcome. MPA-AUC was useful to reduce the rate of rejection.