Mismatches in Gene Deletions and Kidney-related Proteins as Candidates for Histocompatibility Factors in Kidney Transplantation.

Introduction: The genomic mismatch level between donor and recipient may be associated with the risk of rejection and graft survival. We determined the association of genome-level matching with acute rejection in deceased-donor kidney transplantation. Methods: The study cohort consists of 1025 recipient-donor pairs transplanted in a single center from 2007 to 2017 in Helsinki. The associations between the sums of whole-genome missense variant mismatches and missense mismatches in transmembrane, secretory, and kidney-related proteins, with acute rejection were estimated using Cox model. In addition, we analyzed 40 deletion-tagging variants using Cox model. Results: The association analysis between mismatch sums of kidney-related proteins and acute rejection resulted in an unadjusted hazard ratio (HR) of 1.15 (95% confidence interval [CI], 1.01-1.30; P = 0.029) and adjusted HR of 1.13 (95% CI, 0.99-1.28; P = 0.071). In deletion analysis, a mismatch in rs7542235 genotype GG tagging a homozygous deletion at the complement factor H-related (CFHR), proteins locus, predisposed to acute rejection with an unadjusted HR of 3.10 (95% CI, 1.53-6.29; P = 0.002) and adjusted HR of 2.97 (95% CI, 1.46-6.05; P = 0.003). Conclusion: In conclusion, analyses of genome-level mismatches may be useful tools in prediction of transplantation outcome. The relative importance differs between populations, because we found evidence for CFHR deletion but could not replicate the finding of previously reported LIMS1 deletion.