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

Published version
Peer-reviewed

Type

Article

Change log

Authors

Hernandez-Fuentes, Maria P  ORCID logo  https://orcid.org/0000-0002-7558-9441
Franklin, Christopher  ORCID logo  https://orcid.org/0000-0003-3893-0759
Rebollo-Mesa, Irene 
Mollon, Jennifer 
Delaney, Florence 

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.

Description

Keywords

basic (laboratory) research/science, genomics, graft survival, kidney transplantation/nephrology, rejection, translational research/science, Adult, DNA Replication, Female, Genome-Wide Association Study, Genotype, Graft Survival, Histocompatibility Testing, Humans, Kidney Transplantation, Male, Middle Aged, Polymorphism, Single Nucleotide, Tissue Donors, Transplant Recipients, Transplantation, Homologous

Journal Title

Am J Transplant

Conference Name

Journal ISSN

1600-6135
1600-6143

Volume Title

18

Publisher

Elsevier BV
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)