Kidney Res Clin Pract.  2023 May;42(3):389-402. 10.23876/j.krcp.22.061.

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

• Poppelaars F
• Eskandari SK
• Damman J
• Seelen MA
• Faria B
• da Costa MG

• KMID: 2543793
• DOI: http://doi.org/10.23876/j.krcp.22.061

Abstract

Background
Despite current matching efforts to identify optimal donor-recipient pairs for kidney transplantation, alloimmunity remains a major source of late transplant failure. Additional genetic parameters in donor-recipient matching could help improve longterm outcomes. Here, we studied the impact of a non-muscle myosin heavy chain 9 gene (MYH9) polymorphism on allograft failure. Methods: We conducted an 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 associations of the MYH9 genotype with risk of graft failure, biopsy-proven acute rejection (BPAR), and delayed graft function (DGF) were estimated. Results: A trend was seen in the association between the MYH9 polymorphism in the recipient and graft failure (recessive model, p = 0.056), but not for the MYH9 polymorphism in the donor. The AA-genotype MYH9 polymorphism in recipients was associated with higher risk of DGF (p = 0.03) and BPAR (p = 0.021), although significance was lost after adjusting for covariates (p = 0.15 and p = 0.10, respectively). The combined presence of the MYH9 polymorphism in donor-recipient pairs was associated with poor long-term kidney allograft survival (p = 0.04), in which recipients with an AA genotype receiving a graft with an AA genotype had the worst outcomes. After adjustment, this combined genotype remained significantly associated with 15-year death-censored kidney graft survival (hazard ratio, 1.68; 95% confidence interval, 1.05–2.70; p = 0.03). Conclusion: Our results reveal that recipients with an AA-genotype MYH9 polymorphism receiving a donor kidney with an AA genotype have significantly elevated risk of graft failure after kidney transplantation.

Keyword

Genetics; Kidney transplantation; Molecular motor proteins; Nephrology