A Custom Target Next-Generation Sequencing 70-Gene Panel and Replication Study to Identify Genetic Markers of Diabetic Kidney Disease.
Genes (Basel)
; 12(12)2021 12 15.
Article
em En
| MEDLINE
| ID: mdl-34946941
ABSTRACT
Diabetic kidney disease (DKD) has been pointed out as a prominent cause of chronic and end-stage renal disease (ESRD). There is a genetic predisposition to DKD, although clinically relevant loci are yet to be identified. We utilized a custom target next-generation sequencing 70-gene panel to screen a discovery cohort of 150 controls, DKD and DKD-ESRD patients. Relevant SNPs for the susceptibility and clinical evolution of DKD were replicated in an independent validation cohort of 824 controls and patients. A network analysis aiming to assess the impact of variability along specific pathways was also conducted. Forty-eight SNPs displayed significantly different frequencies in the study groups. Of these, 28 with p-values lower than 0.01 were selected for replication. MYH9 rs710181 was inversely associated with the risk of DKD (OR = 0.52 (0.28-0.97), p = 0.033), whilst SOWAHB rs13140552 and CNDP1 rs4891564 were not carried by cases or controls, respectively (p = 0.044 and 0.023). In addition, the RGMA rs1969589 CC genotype was significantly correlated with lower albumin-to-creatinine ratios in the DKD patients (711.8 ± 113.0 vs. 1375.9 ± 474.1 mg/g for TC/TT; mean difference = 823.5 (84.46-1563.0); p = 0.030). No biological pathway stood out as more significantly affected by genetic variability. Our findings reveal new variants that could be useful as biomarkers of DKD onset and/or evolution.
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Texto completo:
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Nefropatias Diabéticas
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Sequenciamento de Nucleotídeos em Larga Escala
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Transcriptoma
Tipo de estudo:
Diagnostic_studies
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Etiology_studies
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Incidence_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Aged
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Female
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Humans
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Male
País/Região como assunto:
Europa
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article