Long- and short-term outcomes in renal allografts with deceased donors: A large recipient and donor genome-wide association study.pdf (998.73 kB)
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Long- and short-term outcomes in renal allografts with deceased donors: A large recipient and donor genome-wide association study.

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journal contribution
posted on 23.08.2019, 15:11 by MP Hernandez-Fuentes, C Franklin, I Rebollo-Mesa, J Mollon, F Delaney, E Perucha, C Stapleton, R Borrows, C Byrne, G Cavalleri, B Clarke, M Clatworthy, J Feehally, S Fuggle, SA Gagliano, S Griffin, A Hammad, R Higgins, A Jardine, M Keogan, T Leach, I MacPhee, PB Mark, J Marsh, P Maxwell, W McKane, A McLean, C Newstead, T Augustine, P Phelan, S Powis, P Rowe, N Sheerin, E Solomon, H Stephens, R Thuraisingham, R Trembath, P Topham, R Vaughan, SH Sacks, P Conlon, G Opelz, N Soranzo, ME Weale, GM Lord, United Kingdom and Ireland Renal Transplant Consortium (UKIRTC) and the Wellcome Trust Case Control Consortium (WTCCC)-3
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.

Funding

Wellcome Trust

History

Citation

American Journal of Transplantation, 2018, 18 (6), pp. 1370-1379

Author affiliation

/Organisation/COLLEGE OF LIFE SCIENCES/School of Medicine/Department of Infection, Immunity and Inflammation

Version

VoR (Version of Record)

Published in

American Journal of Transplantation

Publisher

Wiley

eissn

1600-6143

Acceptance date

13/11/2017

Copyright date

2018

Available date

23/08/2019

Language

en