Long- and short-term outcomes in renal allografts with deceased donors: A large recipient and donor genome-wide association study.
View / Open Files
Authors
Rebollo-Mesa, Irene
Mollon, Jennifer
Delaney, Florence
Borrows, Richard
Clatworthy, Menna
Feehally, John
Fuggle, Susan
Leach, Timothy
Marsh, James
McKane, William
McLean, Adam
Newstead, Charles
Rowe, Peter
Solomon, Ellen
Thuraisingham, Raj
Topham, Peter
Vaughan, Robert
Sacks, Steven H
Opelz, Gerhard
United Kingdom and Ireland Renal Transplant Consortium (UKIRTC) and the Wellcome Trust Case Control Consortium (WTCCC)-3
Publication Date
2018-06Journal Title
Am J Transplant
ISSN
1600-6135
Publisher
Elsevier BV
Volume
18
Issue
6
Pages
1370-1379
Language
eng
Type
Article
Physical Medium
Print-Electronic
Metadata
Show full item recordCitation
Hernandez-Fuentes, M. P., Franklin, C., Rebollo-Mesa, I., Mollon, J., Delaney, F., Perucha, E., Stapleton, C., et al. (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), 1370-1379. https://doi.org/10.1111/ajt.14594
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.
Keywords
United Kingdom and Ireland Renal Transplant Consortium (UKIRTC) and the Wellcome Trust Case Control Consortium (WTCCC)-3, Humans, Histocompatibility Testing, Kidney Transplantation, Transplantation, Homologous, Graft Survival, DNA Replication, Genotype, Polymorphism, Single Nucleotide, Adult, Middle Aged, Tissue Donors, Female, Male, Genome-Wide Association Study, Transplant Recipients
Sponsorship
Wellcome Trust (081020/Z/06/Z)
Department of Health (via National Institute for Health Research (NIHR)) (NIHR BTRU-2014-10027)
European Commission (257082)
Wellcome Trust (091310/Z/10/Z)
Identifiers
External DOI: https://doi.org/10.1111/ajt.14594
This record's URL: https://www.repository.cam.ac.uk/handle/1810/283055
Statistics
Total file downloads (since January 2020). For more information on metrics see the
IRUS guide.