الفهرس 
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Abstract
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.
Immunosuppressant is mandatory for the prevention and treatment of graft rejection. The appropriate choice and use of immunosuppressant is directly related to the survival of liver transplant recipients.
Immunosuppressive agents are required in liver transplantation for induction of immunosuppression in the early phase, maintenance of immunosuppression in the late phase or for the treatment of graft rejection.
FK506 (tacrolimus) is a powerful and selective anti-T-lymphocyte agent. with a mechanism of action similar to that of cyclosporine, it binds to an intracellular receptor and subsequently binds to calcineurine and inhibits the calcineurine pathway that stimulate the transcription factor Nuclear factor of activated T cells (NFAT). Dephosphorylated NF-AT translocate to the nucleus, where it binds to specific DNA sites in the promoter regions of several cytokine genes, including interleukin (IL)-2. Through this series of actions, tacrolimus inhibit transcription of IL-2 thus inhibit proliferation and differentiation of T cells producing immunosuppression.
Permeability glycoprotein (P-gp) is the protein product of ABCB1 gene. It is expressed in the plasma membrane of cells distributed in barrier and elimination organs, where it has protective and excretory functions. It plays an important role in first-pass elimination of orally administered drugs to limit their bioavailability by causing efflux of drugs from the lumen-facing epithelia of the small intestine and colon, and from the bile-facing canaliculi of the liver.
Genetic polymorphisms have been reported to influence ABCB1 activity and/or expression by expressing more miRNA levels of ABCB 1 which will result in increasing levels of expressed p-glycoprotein. The aim of our study was to correlate ABCB1 single nucleotide polymorphisms (SNP) rs1045642 located in exon 26 in the coding region and its effect on tacrolimus dose requirements and trough levels in Egyptian liver transplant recipients.
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 by realtime PCR. Tacrolimus trough level measured using chemiluminescent microparticle immunoassay (CMIA) was evaluated for all the recipients during the first 3 months post transplantation.
The present study revealed statistical significance of CC genotype of the recipients when correlated to the effect on tacrolimus C/D ratio and weight adjusted tacrolimus dose during the first week of the first and second months post transplantation but not during the rest of the study period. 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 2nd, 3rd, and 4th weeks but the results were statistically non-significant. 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.
In 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.