Study of the Effect of ABCB1 Single Nucleotide Polymorphism on Tacrolimus Dose Requirements in Liver Transplant Patients

Abstract

Abstract Background Liver transplantation (LT) is the only effective radical cure for all types of end stage liver diseases. Major advances have been made in the field of liver transplantation due to improvements in surgical techniques and organ conservation as well as optimization of intensive care and immunosuppressive management. Aim of the Work The aim of the present work is to assess the influence of ABCB1 gene polymorphism of liver transplant recipients on blood level and dose requirements of oral tacrolimus, in an attempt to help in designing an individualized tacrolimus regimen for Egyptian liver transplant recipient. Patients and Methods The study included 25 liver transplant recipients and their respective donors. All subjects of this study were subjected to full medical history, Clinical evaluation, Laboratory investigations, and ABCB1 gene polymorphism evaluation by RT-PCR. Tacrolimus trough level was evaluated for all the recipients during the first 3 months post transplantation. Results The present study revealed that the presence of CC genotype was significantly correlated to the effect on tacrolimus C/D ratio and Weight adjusted tacrolimus dose during the first week of the first and 2nd month (Z = -2.108, P < 0.05) but not the 3rd month post transplantation (p-value >0.05). Subjects carrying CC genotype required higher doses of tacrolimus to achieve the desired trough levels compared to subjects carrying CT and TT genotypes. The same effect was observed over the whole period of the study but the results were statistically non-significant (p-value>0.05). Recipients who received liver tissue from donors carrying CC genotype also required higher doses of tacrolimus and reached lower levels of blood tacrolimus trough levels. Conclusion The present study revealed that ABCB1 CC genotype of both recipients and donors of liver transplantation was significantly associated with increased required tacrolimus dose early after liver transplantation reaching statistically significant level in the first week of the first and second months.