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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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The Korean Society of Nephrology
2023-05-01
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| Series: | Kidney Research and Clinical Practice |
| Subjects: | |
| Online Access: | http://www.krcp-ksn.org/upload/pdf/j-krcp-22-061.pdf |
| _version_ | 1797692890558758912 |
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| author | Felix Poppelaars Siawosh K. Eskandari Jeffrey Damman Marc A. Seelen Bernardo Faria Mariana Gaya da Costa |
| author_facet | Felix Poppelaars Siawosh K. Eskandari Jeffrey Damman Marc A. Seelen Bernardo Faria Mariana Gaya da Costa |
| author_sort | Felix Poppelaars |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T02:34:06Z |
| format | Article |
| id | doaj.art-b5072a1c6613454688746a46e0a30fa4 |
| institution | Directory Open Access Journal |
| issn | 2211-9132 2211-9140 |
| language | English |
| last_indexed | 2024-03-12T02:34:06Z |
| publishDate | 2023-05-01 |
| publisher | The Korean Society of Nephrology |
| record_format | Article |
| series | Kidney Research and Clinical Practice |
| spelling | doaj.art-b5072a1c6613454688746a46e0a30fa42023-09-05T01:23:54ZengThe Korean Society of NephrologyKidney Research and Clinical Practice2211-91322211-91402023-05-0142338940210.23876/j.krcp.22.0616223A non-muscle myosin heavy chain 9 genetic variant is associated with graft failure following kidney transplantationFelix Poppelaars0Siawosh K. Eskandari1Jeffrey Damman2Marc A. Seelen3Bernardo Faria4Mariana Gaya da Costa5 Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands Department of Pathology, Erasmus University Medical Center, Rotterdam, the Netherlands Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, the NetherlandsBackground 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.http://www.krcp-ksn.org/upload/pdf/j-krcp-22-061.pdfgeneticskidney transplantationmolecular motor proteinsnephrology |
| spellingShingle | Felix Poppelaars Siawosh K. Eskandari Jeffrey Damman Marc A. Seelen Bernardo Faria Mariana Gaya da Costa A non-muscle myosin heavy chain 9 genetic variant is associated with graft failure following kidney transplantation Kidney Research and Clinical Practice genetics kidney transplantation molecular motor proteins nephrology |
| title | A non-muscle myosin heavy chain 9 genetic variant is associated with graft failure following kidney transplantation |
| title_full | A non-muscle myosin heavy chain 9 genetic variant is associated with graft failure following kidney transplantation |
| title_fullStr | A non-muscle myosin heavy chain 9 genetic variant is associated with graft failure following kidney transplantation |
| title_full_unstemmed | A non-muscle myosin heavy chain 9 genetic variant is associated with graft failure following kidney transplantation |
| title_short | A non-muscle myosin heavy chain 9 genetic variant is associated with graft failure following kidney transplantation |
| title_sort | non muscle myosin heavy chain 9 genetic variant is associated with graft failure following kidney transplantation |
| topic | genetics kidney transplantation molecular motor proteins nephrology |
| url | http://www.krcp-ksn.org/upload/pdf/j-krcp-22-061.pdf |
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