Impact of HMOX1 Genetic Variation in Pancreas Transplant Recipients On Long-Term Graft Outcome
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: A265
Keywords: Gene polymorphism, Hemeoxygenase, Pancreas transplantation, Risk factors
Session Information
Session Name: Poster Session A: Preclinical Immunosuppression and Tolerance
Session Type: Poster Session
Date: Saturday, May 2, 2015
Session Time: 5:30pm-7:30pm
Presentation Time: 5:30pm-7:30pm
Location: Exhibit Hall E
Variation within the heme oxygenase 1 (HMOX1) gene, essential for heme catabolism and a known inflammatory and immune regulator, is proposed to play a role in protecting against loss of renal transplant function. Genetic variation within HMOX1 could affect it cytoprotective properties, increasing the chances of damage to the graft and impacting upon long-term graft function. The objective of this study was to determine if common variants in HMOX1 in pancreas donors and transplant recipients correlated with long-term pancreas graft function in type 1 diabetics. We genotyped 435 pancreas transplant donors and 431 transplant recipients, all of whom had undergone pancreas transplantation at the Oxford Transplant Centre UK, for all common variation in HMOX1 using 6 tag single nucleotide polymorphisms (SNPs). Death-censored cumulative events were analysed using Kaplan-Meier and Cox regression. Presence of rs2071748 AA genotype in our recipients was predictive of reduced long-term graft survival, compared to recipients with AG/GG genotypes (log rank P=0.025), with presence of the rs5755720 GG genotype in our recipients showing a borderline association with reduced long-term graft survival, compared with recipients with AG/AA genotype (log rank P=0.048). Multivariate Cox regression, including donor and recipient transplant variables, confirmed association of rs2071748 AA genotype (P=0.006, HR=2.25; [95% CI=1.26-4.02]) and rs5755720 GG genotype (P=0.018, HR=2.08 [95% CI=1.14-2.08]) with long-term graft function. HMOX1 donor genotype did not show any association with long-term graft function. Our results show, for the first time, preliminary evidence for HMOX1 pancreas transplant recipient genotype in long-term pancreas graft function. Replication in a larger cohort is necessary to confirm these results. Functional analysis will also be required to reveal how these risk genotypes contribute to decreased long-term graft function, potentially providing new opportunities to target this pathway to preserve long-term graft function.
To cite this abstract in AMA style:
Duff C, Hamilton A, Mittal S, Barnardo M, Fuggle S, Friend P, Gough S, Simmonds M. Impact of HMOX1 Genetic Variation in Pancreas Transplant Recipients On Long-Term Graft Outcome [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/impact-of-hmox1-genetic-variation-in-pancreas-transplant-recipients-on-long-term-graft-outcome/. Accessed October 15, 2024.« Back to 2015 American Transplant Congress