Differences in Genetic Variants That Influence Long-Term Graft Function Between Pancreas Transplant Donors and Recipients
1Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), University of Oxford, Oxford, United Kingdom
2Oxford Transplant Centre, Oxford University Hospitals NHS Trust, Oxford, United Kingdom
3Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdom
4Oxford National Institute for Health Research Biomedical Research Centre, Oxford, United Kingdom.
Meeting: 2015 American Transplant Congress
Abstract number: 437
Keywords: Gene polymorphism, Graft function, Pancreas transplantation
Session Information
Session Name: Concurrent Session: Immune Monitoring II
Session Type: Concurrent Session
Date: Tuesday, May 5, 2015
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 May 19, 2025.« Back to 2015 American Transplant Congress