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Long- and short-term outcomes in renal allografts with deceased donors: A large recipient and donor genome-wide association study.

Hernandez-Fuentes, MP; Franklin, C; Rebollo-Mesa, I; Mollon, J; Delaney, F; Perucha, E; Stapleton, C; Borrows, R; Byrne, C; Cavalleri, G; et al. Hernandez-Fuentes, MP; Franklin, C; Rebollo-Mesa, I; Mollon, J; Delaney, F; Perucha, E; Stapleton, C; Borrows, R; Byrne, C; Cavalleri, G; Clarke, B; Clatworthy, M; Feehally, J; Fuggle, S; Gagliano, SA; Griffin, S; Hammad, A; Higgins, R; Jardine, A; Keogan, M; Leach, T; MacPhee, I; Mark, PB; Marsh, J; Maxwell, P; McKane, W; McLean, A; Newstead, C; Augustine, T; Phelan, P; Powis, S; Rowe, P; Sheerin, N; Solomon, E; Stephens, H; Thuraisingham, R; Trembath, R; Topham, P; Vaughan, R; Sacks, SH; Conlon, P; Opelz, G; Soranzo, N; Weale, ME; Lord, GM; United Kingdom and Ireland Renal Transplant Consortium (UKIRTC) (2018) Long- and short-term outcomes in renal allografts with deceased donors: A large recipient and donor genome-wide association study. Am J Transplant, 18 (6). pp. 1370-1379. ISSN 1600-6143 https://doi.org/10.1111/ajt.14594
SGUL Authors: MacPhee, Iain Angus MacGregor

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Abstract

Improvements in immunosuppression have modified short-term survival of deceased-donor allografts, but not their rate of long-term failure. Mismatches between donor and recipient HLA play an important role in the acute and chronic allogeneic immune response against the graft. Perfect matching at clinically relevant HLA loci does not obviate the need for immunosuppression, suggesting that additional genetic variation plays a critical role in both short- and long-term graft outcomes. By combining patient data and samples from supranational cohorts across the United Kingdom and European Union, we performed the first large-scale genome-wide association study analyzing both donor and recipient DNA in 2094 complete renal transplant-pairs with replication in 5866 complete pairs. We studied deceased-donor grafts allocated on the basis of preferential HLA matching, which provided some control for HLA genetic effects. No strong donor or recipient genetic effects contributing to long- or short-term allograft survival were found outside the HLA region. We discuss the implications for future research and clinical application.

Item Type: Article
Additional Information: This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2018 The Authors. American Journal of Transplantation published by Wiley Periodicals, Inc. on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.
Keywords: basic (laboratory) research/science, genomics, graft survival, kidney transplantation/nephrology, rejection, translational research/science, Surgery, 11 Medical And Health Sciences
SGUL Research Institute / Research Centre: Academic Structure > Institute of Medical & Biomedical Education (IMBE)
Journal or Publication Title: Am J Transplant
ISSN: 1600-6143
Language: eng
Dates:
DateEvent
29 May 2018Published
1 February 2018Published Online
13 November 2017Accepted
Publisher License: Creative Commons: Attribution 4.0
Projects:
Project IDFunderFunder ID
090355/A/09/ZWellcome Trusthttp://dx.doi.org/10.13039/100004440
090355/B/09/ZWellcome Trusthttp://dx.doi.org/10.13039/100004440
088849/Z/09/ZWellcome Trusthttp://dx.doi.org/10.13039/100004440
WT098051Wellcome Trusthttp://dx.doi.org/10.13039/100004440
WT091310Wellcome Trusthttp://dx.doi.org/10.13039/100004440
G0600698Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
MR/J006742/1Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
G0802068Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
MR/K002996/1Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
G0801537/ID: 88245Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
R080530Guy's and St Thomas' Charityhttp://dx.doi.org/10.13039/501100000380
R090782Guy's and St Thomas' Charityhttp://dx.doi.org/10.13039/501100000380
HEALTH-F5–2010–260687Seventh Framework Programmehttp://dx.doi.org/10.13039/501100004963
305147: BIO-DrIMSeventh Framework Programmehttp://dx.doi.org/10.13039/501100004963
257082Seventh Framework Programmehttp://dx.doi.org/10.13039/501100004963
HEALTH-F5-2011-282510Seventh Framework Programmehttp://dx.doi.org/10.13039/501100004963
PubMed ID: 29392897
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/109606
Publisher's version: https://doi.org/10.1111/ajt.14594

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