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. 2017 Jan;17(1):201-209.
doi: 10.1111/ajt.13912. Epub 2016 Jul 22.

Genome-Wide Association Study of Acute Renal Graft Rejection

L Ghisdal  1 , C Baron  2 , Y Lebranchu  2 , O Viklický  3 , A Konarikova  3 , M Naesens  4   5 , D Kuypers  4   5 , M Dinic  6 , E Alamartine  6 , G Touchard  7 , T Antoine  7 , M Essig  8 , J P Rerolle  8 , P Merville  9 , J L Taupin  10 , Y Le Meur  11 , A Grall-Jezequel  11 , F Glowacki  12 , C Noël  12 , C Legendre  13 , D Anglicheau  13 , N Broeders  1 , W Coppieters  14 , E Docampo  14 , M Georges  14 , Z Ajarchouh  15 , A Massart  1   15 , J Racapé  16 , D Abramowicz  1   17 , M Abramowicz  15   18
Affiliations

Genome-Wide Association Study of Acute Renal Graft Rejection

L Ghisdal et al. Am J Transplant. 2017 Jan.

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.

Keywords: basic (laboratory) research/science; biomarker; genetics; genomics; immunogenetics; immunosuppression/immune modulation; kidney transplantation/nephrology; microarray/gene array; rejection: T cell mediated (TCMR).

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Figures

Figure 1
Figure 1
Discovery cohort: flowchart of patients included. *Death, lost to follow‐up, graft loss for another reason than rejection. **Not biopsy‐proven, protocol biopsy, borderline not treated, or pure humoral rejection. CNI, calcineurin inhibitor; MM, mismatch; PRA, panel reactive antibody; Tx, transplantation.
Figure 2
Figure 2
Replication cohort: flowchart of patients included. *Death, lost to follow‐up, graft loss for another reason than rejection. **Not biopsy‐proven, protocol biopsy, borderline not treated, or pure humoral rejection. ***Including 951 patients without induction. CNI, calcineurin inhibitor; PRA, panel reactive antibody; Tx, transplantation.
See this image and copyright information in PMC

References

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