Session Time: 4:00pm-5:30pm
Presentation Time: 4:48pm-5:00pm
Location: Terrace IV
Genetic variation in caveolin-1, involved in signal transduction and tissue fibrosis, within pancreas transplant donors has been previously shown to correlate with decreased long-term graft function in type 1 diabetics (T1D). Caveolin-1 variation in pancreas transplant recipients however did not correlate with long-term graft function, suggesting that variation in the donor and recipient's genome could lead to transplant loss by different mechanisms. Genetic contributors to T1D, including CTLA-4, PTPN22, IL-2RA and INS-VNTR, have been well established, however it is currently unknown whether these susceptibility genes impact upon long-term pancreas graft function in T1D pancreas transplant recipients. The aim of this study was to determine if T1D gene variants can predict long-term pancreas graft function. We genotyped 435 pancreas donors and 431 transplant recipients who had undergone pancreas transplantation at the Oxford Transplant Centre, UK, for CTLA-4 rs3087243, PTPN22 rs2476601, IL-2RA rs12251307 and INS-VNTR rs689 single nucleotide polymorphisms. Death-censored cumulative events were analysed using Kaplan-Meier and Cox regression. Presence of CTLA-4 rs3087243 GG genotype in our recipients was predictive of reduced long-term pancreas function compared to recipients with AG or AA genotypes (log rank P=0.007). Multivariate Cox regression, adjusting for donor and recipient transplant factors, confirmed association of the rs3087243 GG genotype (P=0.027, HR=2.28 [95%CI=1.10-4.74]) with long-term graft function. Variation within donor rs3087243 genotype did not predict long-term graft function (log rank P=0.507). No other variant screened predicted long-term graft function. This study provides evidence for recipient CTLA-4 genotype in predicting long-term pancreas graft function. Whilst screening CTLA-4 in other datasets is required to confirm these pilot results, this suggests that variation within the recipient's immune response could represent a recipient specific pathway involved in loss of transplant function.
To cite this abstract in AMA style:Simmonds M, Duff C, Hamilton A, Mittal S, Barnardo M, Fuggle S, Friend P, Gough S. Differences in Genetic Variants That Influence Long-Term Graft Function Between Pancreas Transplant Donors and Recipients [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/differences-in-genetic-variants-that-influence-long-term-graft-function-between-pancreas-transplant-donors-and-recipients/. Accessed February 22, 2020.
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