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

Abstract

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.

Rasagiline Pharmacokinetics in CYP1A2 Variant Healthy Smokers & Non-smokers in Different Doses

“…Where the values were one-third as compared to CC-smokers & non-smokers. These were consistent with the results of Blake CM et al 21 who presented analysis on pharmacokinetics of metaprolol and with Woo 13 who reported influence of genetic polymorphism on pharmacokinetics of drugs. The largest clearance observed in AA smokers group further augments the proposal of making a special strategy for dosing of rasagiline in this particular group.…”

“…The results were consistent with Woo HI et al 12 who found genetic association with pharmacokinetics of atorvastatin and findings of Azam F et al identifying the role of ABCB1 polymorphism in achieving optimal levels of tacrolimus during dose titration. 13 CYP enzymes alter pharmacokinetics of drugs. Javed A reported side effects of chloroquine when given in combination with CYP3A4 inhibitors.…”

“…The results were consistent with Woo HI et al 12 who found genetic association with pharmacokinetics of atorvastatin and findings of Azam F et al identifying the role of ABCB1 polymorphism in achieving optimal levels of tacrolimus during dose titration. 13 …”

Effects of ABCB1 DNA methylation in donors on tacrolimus blood concentrations in recipients following liver transplantation.

“…The P-glycoprotein (P-gp) transporter, which is encoded by theABCB1 transporter gene (also known as the MDR1 gene), is widely distributed in intestinal epithelial cells, liver cells, and renal proximal tubule epithelial cells 1 . Previous studies have shown that ABCB1 may affect tacrolimus absorption, distribution, and excretion 2,3 . Thus, some studies have focused on evaluating the relationship between ABCB1 gene polymorphism (1236C>T, rs1128503, Gly412Gly; 677G>T/A, rs2032582, Ala893DSer/Thr; 3435C>T, rs1045642, Ile1145Ile of exons 12, 21, and 26) and tacrolimus pharmacokinetics 3,4 .…”

“…Previous studies have shown that ABCB1 may affect tacrolimus absorption, distribution, and excretion 2,3 . Thus, some studies have focused on evaluating the relationship between ABCB1 gene polymorphism (1236C>T, rs1128503, Gly412Gly; 677G>T/A, rs2032582, Ala893DSer/Thr; 3435C>T, rs1045642, Ile1145Ile of exons 12, 21, and 26) and tacrolimus pharmacokinetics 3,4 . However, the findings of these studies are inconsistent as concerns both SNPs and haplotypes, and systematic mechanistic studies to support their conclusions are still lacking.…”