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

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 long-term outcomes. Here, we studied the impa...

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Bibliographic Details
Main Authors: Felix Poppelaars, Siawosh K. Eskandari, Jeffrey Damman, Marc A. Seelen, Bernardo Faria, Mariana Gaya da Costa
Format: Article
Language:English
Published: The Korean Society of Nephrology 2023-05-01
Series:Kidney Research and Clinical Practice
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Online Access:http://www.krcp-ksn.org/upload/pdf/j-krcp-22-061.pdf
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Summary: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 long-term 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.
ISSN:2211-9132
2211-9140