Effect of donor non-muscle myosin heavy chain (MYH9) gene polymorphisms on clinically relevant kidney allograft dysfunction

Joanna Pazik,Dominika Dęborska Materkowska,Monika Oldak,Dominika Oziębło,Anna Sadowska,Magdalena Durlik,Jacek Malejczyk

doi:10.1186/s12882-020-02039-6

Joanna Pazik, Dominika Dęborska Materkowska + Show 5 more

Open Access

https://doi.org/10.1186/s12882-020-02039-6

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Abstract

BackgroundDespite 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.MethodsIn 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.ResultsDistribution 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.ConclusionDeceased 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.

Highlights

Despite its established association with chronic kidney disease (CKD) the role of myosin-9 (MYH9) gene variation on transplanted kidney function remains unknown
Myosin-9 heavy chain gene (MYH9) gene polymorphisms were associated with chronic kidney disease in genome wide association studies (GWAS) of Hispanic and European Americans
We found that donor MYH9 rs3752462 C > T polymorphism predicted renal graft estimated glomerular filtration rate (eGFR) with-in 12 months follow up

Summary

Introduction

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. 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 [5,6,7], the role of MYH9 variation in the pathogenesis of chronic kidney disease (CKD) remains. Its functional mutations which cause the socalled MYH9-related disease, may affect the kidneys. MYH9 gene polymorphisms were associated with chronic kidney disease in genome wide association studies (GWAS) of Hispanic and European Americans. Pattaro found an association of SNPs within the MYH9 gene and serum creatinine concentrations in three isolated European populations: rs2239784 and rs5756168 in MICROS cohort (The Genetic Study of three Population Microisolates in South Tyrol), rs136211 in VIS cohort (CROATIAVis study) and rs11089788 in the metaanalysis of three studied populations (MICROS, VIS and ERF cohort, Erasmus Rucphen Family study) [12]

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