Background Cyclosporin A （CsA） is a substrate of both cytochrome P450 3A （CYP3A） and P-glycoprotein （P-gp）, some of the single nucleotide polymorphisms （SNPs） in these genes are associated with interindividual...Background Cyclosporin A （CsA） is a substrate of both cytochrome P450 3A （CYP3A） and P-glycoprotein （P-gp）, some of the single nucleotide polymorphisms （SNPs） in these genes are associated with interindividual variations in CsA pharmacokinetics. We studied the influence of these SNPs on the incidence of rejection and CsA nephrotoxicity, as well as pneumonia within one year after renal transplant and post-transplantation diabetes mellitus （PTDM）, in order to find whether genetic evaluation may help to identify patients at risk and to modulate CsA therapy to optimize graft and patient outcomes. Methods A total of 208 renal transplant recipients receiving CsA were genotyped for ABCB1 （C1236T, G2677T/A, and C3435T）, CYP3A4＊IG, and CYP3A5＊3 by direct sequencing method. Retrospective case control study was utilized to identify the association between CYP3A4＊IG, CYP3A5＊3, ABCB1 genetic polymorphisms and CsA-related outcomes. Results The patients with a CYP3A4＊1G/＊1G genotype were found to have a higher incidence of acute rejection compared with those with CYP3A4＊1/＊1. Conclusion CYP3A4＊1G/＊1G genotype predict increased risk of acute rejection, so genetic evaluation may partly help to identify patients at risk and to modulate CsA therapy to optimize graft and patient outcomes.展开更多
AIM:To investigate the evidence of homogeneous phenomenon on CYP3A5*3 MDR1-3435 and CYP3A4*18of the liver graft after living donor liver transplantation(LDLT).METHODS:We identified the proportional change of the CYP3... AIM:To investigate the evidence of homogeneous phenomenon on CYP3A5*3 MDR1-3435 and CYP3A4*18of the liver graft after living donor liver transplantation(LDLT).METHODS:We identified the proportional change of the CYP3A5*3,MDR1-3435 and CYP3A4*18 from the peripheral blood mononuclear cell of 41 pairs recipient/donor with different genotype polymorphisms and 119liver graft biopsy samples used with the pyrosequencing technique after LDLT.Polymerase chain reaction/ligase detection reaction assay and restriction fragment length polymorphism was employed for genotyping the CYP3A5*3 and CYP3A4*18 single nucleotide poly-morphisms(SNPs).All of the recipients and donors expressed with the similar SNP genotype of CYP3A5*3,MDR1-3435 or CYP3A4*18 were excluded.RESULTS:The final genetic polymorphisms of the liver graft biopsy samples of CYP3A5*3,MDR1-3435 and CYP3A4*18 was predominated depends on the donor with restriction fragment length polymorphism and seems to be less related to the recipient.The proportional changes of G to A alleles of the 119 samples of CYP3A5*3(included A】A/G,A/G】A,A/G】G,G】A,G】A/G and A】G),C to T alleles of the 108 samples of MDR1-3435(included C】C/T,C/T】C,C/T】T,T】C/T and T】C),and T to C alleles of 15 samples of CYP3A4*18(included T/C】T and T】C/T)were significant different between the recipients and the liver graft biopsy samples(P【0.0001)and less difference when compared with the donors in the pyrosequencing analysis after LDLT.CONCLUSION:The CYP3A5*3,MDR1-3435 and CYP3A4*18 of the recipient could be modified by the donor so-called homogenous phenomenon when the recipient’s blood drained into the liver graft.展开更多
文摘Background Cyclosporin A （CsA） is a substrate of both cytochrome P450 3A （CYP3A） and P-glycoprotein （P-gp）, some of the single nucleotide polymorphisms （SNPs） in these genes are associated with interindividual variations in CsA pharmacokinetics. We studied the influence of these SNPs on the incidence of rejection and CsA nephrotoxicity, as well as pneumonia within one year after renal transplant and post-transplantation diabetes mellitus （PTDM）, in order to find whether genetic evaluation may help to identify patients at risk and to modulate CsA therapy to optimize graft and patient outcomes. Methods A total of 208 renal transplant recipients receiving CsA were genotyped for ABCB1 （C1236T, G2677T/A, and C3435T）, CYP3A4＊IG, and CYP3A5＊3 by direct sequencing method. Retrospective case control study was utilized to identify the association between CYP3A4＊IG, CYP3A5＊3, ABCB1 genetic polymorphisms and CsA-related outcomes. Results The patients with a CYP3A4＊1G/＊1G genotype were found to have a higher incidence of acute rejection compared with those with CYP3A4＊1/＊1. Conclusion CYP3A4＊1G/＊1G genotype predict increased risk of acute rejection, so genetic evaluation may partly help to identify patients at risk and to modulate CsA therapy to optimize graft and patient outcomes.
基金Supported by A grant from Chang Gung Memorial Hospital,CMRPG8A0631 to Chiu KW of Taiwan
文摘 AIM:To investigate the evidence of homogeneous phenomenon on CYP3A5*3 MDR1-3435 and CYP3A4*18of the liver graft after living donor liver transplantation(LDLT).METHODS:We identified the proportional change of the CYP3A5*3,MDR1-3435 and CYP3A4*18 from the peripheral blood mononuclear cell of 41 pairs recipient/donor with different genotype polymorphisms and 119liver graft biopsy samples used with the pyrosequencing technique after LDLT.Polymerase chain reaction/ligase detection reaction assay and restriction fragment length polymorphism was employed for genotyping the CYP3A5*3 and CYP3A4*18 single nucleotide poly-morphisms(SNPs).All of the recipients and donors expressed with the similar SNP genotype of CYP3A5*3,MDR1-3435 or CYP3A4*18 were excluded.RESULTS:The final genetic polymorphisms of the liver graft biopsy samples of CYP3A5*3,MDR1-3435 and CYP3A4*18 was predominated depends on the donor with restriction fragment length polymorphism and seems to be less related to the recipient.The proportional changes of G to A alleles of the 119 samples of CYP3A5*3(included A】A/G,A/G】A,A/G】G,G】A,G】A/G and A】G),C to T alleles of the 108 samples of MDR1-3435(included C】C/T,C/T】C,C/T】T,T】C/T and T】C),and T to C alleles of 15 samples of CYP3A4*18(included T/C】T and T】C/T)were significant different between the recipients and the liver graft biopsy samples(P【0.0001)and less difference when compared with the donors in the pyrosequencing analysis after LDLT.CONCLUSION:The CYP3A5*3,MDR1-3435 and CYP3A4*18 of the recipient could be modified by the donor so-called homogenous phenomenon when the recipient’s blood drained into the liver graft.
