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Long‐ and short‐term outcomes in renal allografts with deceased donors: A large recipient and donor genome‐wide association study
Author(s) -
HernandezFuentes Maria P.,
Franklin Christopher,
RebolloMesa Irene,
Mollon Jennifer,
Delaney Florence,
Perucha Esperanza,
Stapleton Caragh,
Borrows Richard,
Byrne Catherine,
Cavalleri Gianpiero,
Clarke Brendan,
Clatworthy Menna,
Feehally John,
Fuggle Susan,
Gagliano Sarah A.,
Griffin Sian,
Hammad Abdul,
Higgins Robert,
Jardine Alan,
Keogan Mary,
Leach Timothy,
MacPhee Iain,
Mark Patrick B.,
Marsh James,
Maxwell Peter,
McKane William,
McLean Adam,
Newstead Charles,
Augustine Titus,
Phelan Paul,
Powis Steve,
Rowe Peter,
Sheerin Neil,
Solomon Ellen,
Stephens Henry,
Thuraisingham Raj,
Trembath Richard,
Topham Peter,
Vaughan Robert,
Sacks Steven H.,
Conlon Peter,
Opelz Gerhard,
Soranzo Nicole,
Weale Michael E.,
Lord Graham M.
Publication year - 2018
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/ajt.14594
Subject(s) - medicine , immunosuppression , human leukocyte antigen , immunology , genome wide association study , immune system , histocompatibility testing , kidney transplantation , genetic association , transplantation , genetics , antigen , genotype , gene , single nucleotide polymorphism , biology
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.