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Title: Genome-Wide Association Study of Acute Renal Graft Rejection
Authors: Ghisdal, L ×
Baron, C
Lebranchu, Y
Viklický, O
Konarikova, A
Naesens, Maarten
Kuypers, Dirk
Dinic, M
Alamartine, E
Touchard, G
Antoine, T
Essig, M
Rerolle, J P
Merville, P
Taupin, J L
Le Meur, Y
Grall-Jezequel, A
Glowacki, F
Noël, C
Legendre, C
Anglicheau, D
Broeders, N
Coppieters, W
Docampo, E
Georges, M
Ajarchouh, Z
Massart, A
Racapé, J
Abramowicz, D
Abramowicz, M #
Issue Date: Jun-2016
Publisher: Munksgaard International Publishers
Series Title: American Journal of Transplantation vol:Ahead of print
Article number: 10.1111/ajt.13912
Abstract: Acute renal rejection is a major risk factor for chronic allograft dysfunction and long-term graft loss. We performed a genome-wide association study to detect loci associated with biopsy-proven acute T cell-mediated rejection occurring in the first year after renal transplantation. In a discovery cohort of 4127 European renal allograft recipients transplanted in eight European centers, we used a DNA pooling approach to compare 275 cases and 503 controls. In an independent replication cohort of 2765 patients transplanted in two European countries, we identified 313 cases and 531 controls, in whom we genotyped individually the most significant single nucleotide polymorphisms (SNPs) from the discovery cohort. In the discovery cohort, we found five candidate loci tagged by a number of contiguous SNPs (more than five) that was never reached in iterative in silico permutations of our experimental data. In the replication cohort, two loci remained significantly associated with acute rejection in both univariate and multivariate analysis. One locus encompasses PTPRO, coding for a receptor-type tyrosine kinase essential for B cell receptor signaling. The other locus involves ciliary gene CCDC67, in line with the emerging concept of a shared building design between the immune synapse and the primary cilium.
URI: 
ISSN: 1600-6135
Publication status: accepted
KU Leuven publication type: IT
Appears in Collections:Laboratory of Nephrology
× corresponding author
# (joint) last author

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