Impact Of Genetic Polymorphisms On Tacrolimus Trough Blood Concentration
In Chinese Liver Transplant Recipients
Abstract
Abstract Purpose: The aim of this study was to analyze the effect of
various genetic polymorphisms and clinical factors on TAC concentration
in convalescence period (CP) and stabilization period (SP) post liver
transplantation. Patients and Methods: A total 13 SNPs of CYP3A4,
CYP3A5, CYP3A7, SLCO1B1, POR, ABCB1, C5 and C6 were genotyped in 97
Chinese liver transplant recipients. Associations between SNPs and TAC
concentration/dose ratio (C0/D) were analyzed using different genetic
models in both CP and SP. Multivariate linear regression was used to
analyze associations between TAC log (C0/D) and clinical factors.
Results: We discovered that the effects of genetic variants and clinical
factors differed between the two periods as liver function gradually
recovered. We identified CYP3A5 (rs15524), C6 (rs9200) along with ALB
and Cr as independent predictors of TAC C0/D. In addition our final
model inclusive of ALB, Cr, rs15524 and rs9200 explained a total of
30.5% variance in TAC log (C0/D). Conclusion: The results of our study
suggest that in the early stages post transplantation surgery recipient
genetic and clinical factors exert a short term impact on TAC metabolism
which gradually decreases with time.