Impact of HMOX1 Genetic Variation in Pancreas Transplant Recipients On Long-Term Graft Outcome

C. Duff,¹ A. Hamilton,¹ S. Mittal,^2,3,4 M. Barnardo,^2,3 S. Fuggle,^2,3 P. Friend,^2,3 S. Gough,^1,4 M. Simmonds.¹

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 November 21, 2024.

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