Effect of donor non-muscle myosin heavy chain (MYH9) gene polymorphisms on clinically relevant kidney allograft dysfunction.
Adolescent
Adult
Aged
Cadaver
Female
Genotype
Glomerular Filtration Rate
Humans
Kidney Failure, Chronic
/ surgery
Kidney Transplantation
Longitudinal Studies
Male
Middle Aged
Myosin Heavy Chains
/ genetics
Polymorphism, Single Nucleotide
Postoperative Complications
/ epidemiology
Proteinuria
/ epidemiology
Renal Insufficiency
/ epidemiology
Tissue Donors
Young Adult
Estimated glomerular filtration rate
Genetic biomarker
Kidney transplantation
MYH9
Proteinuria
SNP
Journal
BMC nephrology
ISSN: 1471-2369
Titre abrégé: BMC Nephrol
Pays: England
ID NLM: 100967793
Informations de publication
Date de publication:
01 09 2020
01 09 2020
Historique:
received:
21
03
2020
accepted:
23
08
2020
entrez:
3
9
2020
pubmed:
3
9
2020
medline:
21
10
2021
Statut:
epublish
Résumé
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. 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. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 32873246
doi: 10.1186/s12882-020-02039-6
pii: 10.1186/s12882-020-02039-6
pmc: PMC7465840
doi:
Substances chimiques
MYH9 protein, human
0
Myosin Heavy Chains
EC 3.6.4.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
380Subventions
Organisme : Ministerstwo Nauki i Szkolnictwa Wyższego
ID : NN402426633, NN402566850
Pays : International
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