Long‐ and short‐term outcomes in renal allografts with deceased donors: a large recipient and donor genome‐wide association study

Hernandez-Fuentes, M. P. et al. (2018) Long‐ and short‐term outcomes in renal allografts with deceased donors: a large recipient and donor genome‐wide association study. American Journal of Transplantation, 18(6), pp. 1370-1379. (doi: 10.1111/ajt.14594) (PMID:29392897)

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: Articles
• Additional Information: Supported by grants awarded from the Wellcome Trust (090355/A/09/Z, 090355/B/09/Z and 088849/Z/09/Z, “WTCCC3”), the Medical Research Council (grants G0600698 and MR/J006742/1 to S.H.S.; G0802068 to G.M.L. and MR/K002996/1 to G.M.L; grants G0801537/ID: 88245), Guy’s and St Thomas’ Charity (grants R080530 and R090782) to M.H.F. and G.M.L., from the European Union FP7 (grant agreement no HEALTH- F5–2010–260687 to M.H.F. and pro- ject number 305147: BIO- DrIM to M.H.F. and I.R.M.); and by the National Institute for Health Research Biomedical Research Centre at Guy’s and St Thomas’ and King’s College London. Anonymized clinical data were also provided NIHR Health Informatics Collaborative. N.S.’s research is supported by the Wellcome Trust (Grant Codes WT098051 and WT091310), the EU FP7 (EPIGENESYS Grant Code 257082 and BLUEPRINT Grant Code HEALTH- F5- 2011- 282510) and the National Institute for Health Research Blood and Transplant Research Unit (NIHR BTRU) in Donor Health and Genomics at the University of Cambridge in partnership with NHS Blood and Transplant (NHSBT).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Mark, Professor Patrick and Jardine, Professor Alan
• Authors: Hernandez-Fuentes, M. P., 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, S. A., Griffin, S., Hammad, A., Higgins, R., Jardine, A., Keogan, M., Leach, T., MacPhee, I., Mark, P. B., 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, S. H., Conlon, P., Opelz, G., Soranzo, N., Weale, M. E., and Lord, G. M.
• Subjects: R Medicine > RC Internal medicine
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: American Journal of Transplantation
• Publisher: Wiley
• ISSN: 1600-6135
• ISSN (Online): 1600-6143
• Published Online: 01 February 2018
• Copyright Holders: Copyright © 2018 The Authors
• First Published: First published in American Journal of Transplantation 18(6):1370-1379
• Publisher Policy: Reproduced under a Creative Commons License