A non-muscle myosin heavy chain 9 genetic variant is associated with graft failure following kidney transplantation

Abstract

AbstractBackgroundDespite current matching efforts to identify optimal donor-recipient pairs in kidney transplantation, alloimmunity remains a major proponent of late transplant failure. While kidney allocation based on human leukocyte antigen (HLA) matching has markedly prolonged short-term graft survival, new data suggests that additional genetic parameters in donor-recipient matching could help improve the long-term outcomes. Here, we studied the impact of a recently discovered non-muscle myosin heavy chain 9 gene (MYH9) polymorphism on kidney allograft failure.MethodsWe conducted a prospective observational cohort study, analyzing the DNA of 1,271 kidney donor-recipient transplant pairs from a single academic hospital for the MYH9 rs11089788 C>A polymorphism. The association of the MYH9 genotype with the risk of graft failure (primary outcome), biopsy-proven acute rejection (BPAR), and delayed graft function (DGF) (secondary outcomes) were determined.ResultsThe MYH9 polymorphism in the donor was not associated with 15-year death-censored kidney graft survival, whereas a trend was seen for the association between the MYH9 polymorphism in the recipient and graft failure (recessive model, P=0.056). Having the AA-genotype of the MYH9 polymorphism in recipients was associated with a higher risk of DGF (P=0.031) and BPAR (P=0.021), although the significance was lost after adjustment for potential confounders (P=0.15 and P=0.10, respectively). The combined presence of the MYH9 polymorphism in donor-recipient pairs was significantly associated with long-term kidney allograft survival (P=0.036), in which recipients with an AA-genotype receiving a graft with an AA-genotype had the worst outcome. After adjustment for covariates, this combined genotype remained significantly associated with 15-year death-censored kidney graft survival (HR 1.68, 95%-CI: 1.05 – 2.70, P=0.031).ConclusionsOur results reveal that recipients with an AA-genotype MYH9 polymorphism receiving a donor kidney with an AA-genotype, have a significantly elevated risk of graft failure after kidney transplantation.Key pointsIn recipients, the MYH9 SNP was associated with delayed graft function and biopsy-proven acute rejection after kidney transplantation, although the significance was lost in multivariable analysis.Presence of the MYH9 variant in both the donor and recipient significantly associated with long-term kidney allograft survival in multivariable analysis.Our present findings suggests that matching donor-recipient transplant pairs based on the MYH9 polymorphism may attenuate the risk of graft loss.