Effect of donor non-muscle myosin heavy chain ( MYH9 ) gene polymorphisms on clinically relevant kidney allograft dysfun
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RESEARCH ARTICLE
Open Access
Effect of donor non-muscle myosin heavy chain (MYH9) gene polymorphisms on clinically relevant kidney allograft dysfunction Joanna Pazik1* , Monika Oldak2, Dominika Oziębło2,3, Dominika Dęborska Materkowska1, Anna Sadowska1, Jacek Malejczyk2 and Magdalena Durlik1
Abstract Background: Despite its established association with chronic kidney disease (CKD) the role of myosin-9 (MYH9) gene variation on transplanted kidney function remains unknown. This study aimed at evaluating the effect of donor MYH9 nephrogenic variants on renal allograft function within the first post transplantation year. Methods: In the longitudinal kidney transplant study 207 deceased donors were genotyped for previously known risk MYH9 single nucleotide polymorphisms (SNPs). The predictor was MYH9 high–risk variants status. The primary outcome was mean eGFR found in low vs. high risk MYH9 genotypes between third and twelfth post-transplant month, the secondary outcome was the risk of proteinuria. Results: Distribution of genotypes remained in Hardy-Weinberg equilibrium. The T allele of rs3752462 (dominant model, TT or TC vs. CC) was associated with higher filtration rate (P = 0.05) in a multivariate analysis after adjusting for delayed graft function and donor sex. Two G alleles of rs136211 (recessive model, GG vs. GA or AA) resulted in doubling the risk of proteinuria (OR = 2.22; 95% CI = 1.18–4.37, P = 0.017) after adjusting for donor and recipient sex. Conclusion: Deceased donor kidneys of European descent harboring MYH9 SNPs rs3752462 T allele show significantly superior estimated filtration rate while those of rs136211 GG genotype excessive risk of proteinuria. These findings, if replicated, may further inform and improve individualization of allocation and treatment policies. Keywords: MYH9, Genetic biomarker, SNP, Kidney transplantation, Estimated glomerular filtration rate, Proteinuria
Background Growing insight on how genetic variants of interest are linked to transplantation outcomes, give promise that screening genomes of organ recipients and donors would improve prediction of allograft longevity. In consequence novel targets for intervention, especially in organ allocation * Correspondence: [email protected] 1 Department of Transplantation Medicine, Nephrology and Internal Diseases, Medical University of Warsaw, 59 Nowogrodzka Street, 02-006 Warsaw, Poland Full list of author information is available at the end of the article
policies or immunosuppressive regimen adjustments would be provided [1, 2]. Nonmuscle myosin heavy chain II-A (NMMHC-IIA) is a universal contractile protein encoded by MYH9 gene and expressed in muscle and non-muscle cells that engage in maintaining cell shape, adhesion, and division [3]. Despite growing evidence of the expression of NMMHC-IIA in the kidney tissue [4, 5], as well as its important function in podocytes cytoskeletal organization, cell adhesion, traction and motility [5–7], the role of MYH9 variation in the pathogenesis of chronic kidney disease (CKD) remains
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