The Impact of ABCC2 -24C>T Gene Polymorphism on Graft Survival in Kidney Transplant Recipients

Abstract

Personalized medicine in kidney transplantation has the potential to improve outcomes and reduce complications. The aim of this study was to investigate the influence of single nucleotide polymorphisms in genes encoding metabolizing enzymes (CYP3A5) and transporters (ABCC2) on clinical outcomes (acute graft failure and/or acute tubular necrosis (ATN)) in kidney transplant recipients (KTR). This was a multicenter, retrospective cohort study where adult KTR who had undergone kidney transplantation between 2020 and 2021 and received tacrolimus-mycophenolate treatment were enrolled in the study. DNA was extracted from collected blood samples using a commercially available kit. CYP3A5*3, ABCC2 -24C>T and ABCC2 3972C>T SNP were determined by polymerase chain reaction. Of the total 39 patients included, nine (23.1%) KTR had an incidence of acute graft failure and/or ATN. A multiple logistic regression showed wildtype ABCC2 -24C>T C allele had a higher risk of developing acute graft rejection and/or ATN compared to the variant allele carriers (adjusted Odd Ratios [aOR]: 27.675, p = 0.038). Recipients who had delayed graft function (aOR: 49.214, p = 0.012) and a history of CMV infection (aOR: 18.097, p = 0.009) were at 49.2 and 18.1-times increased risk for acute graft failure and/or ATN, respectively. The large aOR was inevitable due to the small sample size and required cautious interpretation. This is the first study to determine the effect of the ABCC2 -24C>T genetic polymorphism on clinical outcomes in Malaysian KTR and forms the basis for further work on ABCC2 -24C>T effects in long-term KTR.