Library Dissertation Showcase

The role genetic variations in CYP3A4 and alterations in Caveolin-1 function play within long-term pancreas and kidney transplant function

  • Year of Publication:
  • 2021

As cases of type 1 diabetes continue to rise globally, clinicians and scientists are looking to improve post-transplant pancreatic and kidney graft function. Previous research highlighted that immunosuppressants have a toxic impact upon graft function; possibly due to genetic variations in drug metabolism enzymes, or the drugs interactions with Caveolin-1 (Cav1). The aim of this study was to examine whether common variations of single nucleotide polymorphisms in drug metabolism genes (Cytochrome P450 3A4 (CYP3A4)) correlate with pancreatic transplant outcome, but also observe the toxic effects that an immunosuppressive environment has upon Cav1 in pancreatic and kidney cell lines. Genetic analysis of CYP3A4 and its variations using Kaplan-Meier reported no significance in its correlation with allograft function: RS2740574 (P=0.565 – 0.839), RS2246709 (P=0.331 – 0.439), RS464347 (P=0.956 – 0.974). Similarly, univariate analysis reported no significance, however clinical features, such as operation type, showed significance (P= 0.001 – 0.037) correlating with previously published research. An immunosuppressive environment was induced upon pancreatic and kidney cells using Tacrolimus, and western blotting revealed a significant loss in the Cav1 protein, even at low dosing quantities. This indicates that the toxicity of immunosuppressants can impact upon Cav1 and consequently long-term allograft functions, supporting previous work.

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