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

Abstract

BackgroundDespite 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.

Synergistic impact of three complement polymorphisms in the donor, not the recipient, on long-term kidney allograft survival

“…Patients receiving a first single kidney transplantation at the University Medical Center Groningen (UMCG) between March 1993 and February 2008 were selected for this study. [31][32][33][34][35][36] Subsequent, exclusion criteria consisted of perioperative technical complications (3 pairs excluded), lack of available DNA (65 pairs excluded), loss of follow-up (4 pairs excluded), retransplantation at the time of recruitment (22 pairs excluded) and simultaneous transplantation of other organs (65 pairs excluded). In summary, we began with 1430 kidney transplant pairs, and after applying exclusion criteria, we included 1271 kidney transplant pairs in this study.…”

An interleukin 6-based genetic risk score strengthened with interleukin 10 polymorphisms associated with long-term kidney allograft outcomes

“…Patients receiving a single kidney transplantation at the University Medical Center Groningen (UMCG) between March 1993 and February 2008 were included. Exclusion criteria consisted of perioperative, technical complications, lack of available DNA, loss of follow‐up, and re‐transplantation at the time of recruitment 27–33 . The primary endpoint was 15‐year death‐censored graft survival.…”

“…Exclusion criteria consisted of perioperative, technical complications, lack of available DNA, loss of follow‐up, and re‐transplantation at the time of recruitment. 27 , 28 , 29 , 30 , 31 , 32 , 33 The primary endpoint was 15‐year death‐censored graft survival.…”