Evaluation of CD86 gene polymorphism at +1057 position in liver transplant recipients

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. We aimed 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. The study included 25 liver transplant recipients and their respective 25 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 concentration 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 months (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.

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Influence of ABCB1 gene polymorphism on concentration to dose ratio and adverse effects of tacrolimus in Pakistani liver transplant recipients

Pakistan Journal of Medical Sciences ◽

10.12669/pjms.37.3.3898 ◽

2021 ◽

Vol 37 (3) ◽

Author(s):

Fahad Azam ◽

Moosa Khan ◽

Tanwir Khaliq ◽

Abubakar Hafeez Bhatti

Keyword(s):

Adverse Effects ◽

Gene Polymorphism ◽

Liver Transplant ◽

Dose Titration ◽

Transplant Recipients ◽

Dose Ratio ◽

Post Transplantation ◽

Abcb1 Gene ◽

Liver Transplant Recipients ◽

Trough Levels

Objective: To evaluate the possible association of ABCB1 single nucleotide polymorphism (SNPs) of the ABCB1 gene with tacrolimus dosages, concentration-to-dose ratios (CDR) and adverse effects in Pakistani liver transplant recipients. Methods: This observational study was conducted at Shifa International Hospital, Shifa Tameer-e-Millat University, Islamabad and Basic Medical Sciences Institute, Karachi from September 2016 to July 2020. Eighty-one liver transplant recipients were included. Demographics, clinical data, tacrolimus trough levels and doses were monitored. Electrochemiluminescence immunoassay (ECLIA) was used to measure tacrolimus trough levels. Transplant recipients were genotyped for three ABCB1 SNPs (rs1045642, rs2032582 and rs1128503). Acute cellular rejection (ACR), sepsis and other adverse events were monitored. Results: ABCB1 rs1045642 CC genotype showed lower tacrolimus CDR as compared to CT and TT genotype in the first week of the post-transplantation period (p=0.02). There was a significant association of polymorphisms in rs1045642, rs2032582 and rs1128503 with psychosis, sepsis and ACR respectively. Conclusion: Identification of ABCB1 rs1045642 polymorphism may shorten the time to achieve optimum levels of tacrolimus during dose titration. ABCB1 polymorphism rs1045642, rs2032582 and rs1128503 may predict adverse effects in liver transplant recipients receiving tacrolimus. doi: https://doi.org/10.12669/pjms.37.3.3898 How to cite this:Azam F, Khan M, Khaliq T, Bhatti ABH. Influence of ABCB1 gene polymorphism on concentration to dose ratio and adverse effects of tacrolimus in Pakistani liver transplant recipients. Pak J Med Sci. 2021;37(3):---------. doi: https://doi.org/10.12669/pjms.37.3.3898 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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