| Autor: |
Consortium, Claire Hill, Seamus Duffy, Laura M. Kettyle, Liane McGlynn, Niina Sandholm, Rany M. Salem, Alex Thompson, Elizabeth J. Swan, Jill Kilner, Peter Rossing, Paul G. Shiels, Maria Lajer, Per-Henrik Groop, Alexander Peter Maxwell, Amy Jayne McKnight, on behalf of the GENIE Consortium on behalf of the GENIE |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
Genes; Volume 14; Issue 5; Pages: 1029 |
| ISSN: |
2073-4425 |
| DOI: |
10.3390/genes14051029 |
| Popis: |
Diabetic kidney disease (DKD) represents a major global health problem. Accelerated ageing is a key feature of DKD and, therefore, characteristics of accelerated ageing may provide useful biomarkers or therapeutic targets. Harnessing multi-omics, features affecting telomere biology and any associated methylome dysregulation in DKD were explored. Genotype data for nuclear genome polymorphisms in telomere-related genes were extracted from genome-wide case–control association data (n = 823 DKD/903 controls; n = 247 end-stage kidney disease (ESKD)/1479 controls). Telomere length was established using quantitative polymerase chain reaction. Quantitative methylation values for 1091 CpG sites in telomere-related genes were extracted from epigenome-wide case–control association data (n = 150 DKD/100 controls). Telomere length was significantly shorter in older age groups (p = 7.6 × 10−6). Telomere length was also significantly reduced (p = 6.6 × 10−5) in DKD versus control individuals, with significance remaining after covariate adjustment (p = 0.028). DKD and ESKD were nominally associated with telomere-related genetic variation, with Mendelian randomisation highlighting no significant association between genetically predicted telomere length and kidney disease. A total of 496 CpG sites in 212 genes reached epigenome-wide significance (p ≤ 10−8) for DKD association, and 412 CpG sites in 193 genes for ESKD. Functional prediction revealed differentially methylated genes were enriched for Wnt signalling involvement. Harnessing previously published RNA-sequencing datasets, potential targets where epigenetic dysregulation may result in altered gene expression were revealed, useful as potential diagnostic and therapeutic targets for intervention. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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