Tacrolimus dose requirement in relation to donor and recipient ABCB1 and CYP3A5 gene polymorphisms in Chinese liver transplant patients

Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society
Wang Wei-linYan Sheng

Abstract

The aim of this study was to investigate whether the heterogeneity in tacrolimus dose requirement is associated with ABCB1 and CYP3A5 gene polymorphisms in Chinese liver transplant patients during the first month after transplantation. ABCB1 and CYP3A5 genotyping was performed using the polymerase chain reaction restriction sites polymorphism-based procedure in Chinese liver transplant recipients (n = 50) and their corresponding donors (n = 50). Tacrolimus whole-blood trough concentrations were measured by immunoassays on the IMx analyzers (Abbott Diagnostics Laboratories, Abbott-Park, IL). Doses required to achieve target blood concentrations and dose-adjusted trough concentrations (concentration/dose [C/D] ratios) were compared among patients according to allelic status of ABCB1 and CYP3A5. The ABCB1 3435CC was observed in 23 subjects (23%), whereas 64 (64%) carried 3435CT and 13 (13%) carried 3435TT. The CYP3A5*1/*1 was observed in 13 subjects (13%), 50 (50%) carried *1/*3, and 37 (37%) carried*3/*3. The tacrolimus C/D ratios were obviously lower in recipients carrying ABCB1 3435CC genotype. For CYP3A5, recipients who received organs from CYP3A5*3/*3 donors had higher C/D ratios. But the donors' ABCB1 and recipients' CYP3A5 ...Continue Reading

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Citations

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