Hypermethylierte DNA als Biomarker für Herz- und Nierenerkrankungen

Hypermethylated DNA as biomarker for heart and kidney disease

by Christin Eller
Doctoral thesis
Date of Examination:2023-07-05
Date of issue:2023-06-28
Advisor:Prof. Dr. Elisabeth Zeisberg
Referee:PD Dr. Moritz Thomas Schnelle
Referee:Prof. Dr. Margarete Schön
Persistent Address: http://dx.doi.org/10.53846/goediss-9970

 

 

Files in this item

Name:Dissertation_Christin_Eller_Bibliothek.pdf
Size:3.50Mb
Format:PDF
Description:Dissertation_Christin_Eller

The following license files are associated with this item:

Abstract

English

Chronic kidney diseases are an increasing medical challenge. Based on the pathophysiology of fibrogenesis, the progression of chronic kidney disease is often characterised by excessive fibroblast activation and parenchymal remodelling mechanisms, which finally lead to fibrosis and renal dysfunction. Fibrosis is influenced by epigenetic regulatory mechanisms. In animal models, aberrant methylation of promoter fragments of RASAL1 caused transcriptional loss of RASAL1 thus contributing to the development of fibrosis. In this study, genomic DNA extracted from whole blood was analysed by using MeDIP and real-time PCR to determine if aberrant RASAL1 promoter methylation is detectable in the blood of patients with kidney disease. In order to identify a potential biomarker, correlations between methylated RASAL1 DNA and laboratory parameters were investigated. Significant hypermethylation of RASAL1 promoter fragments was detected in the blood of patients with kidney disease. Furthermore, an increasing impairment of renal function was significantly associated with an accumulation of methylated RASAL1 DNA. In this context, a decrease in eGFR proved to be a meaningful parameter. In supplementary analyses, hypermethylation of the promoter fragments was also found for the genes PAX3 and RELAXIN3. Methylated DNA of PAX3 and RELAXIN3 accumulated with increasing renal dysfunction. In case of renal anaemia, patients with moderate restriction of kidney function showed only minor changes in the methylated promoter fragments of EPO. Regarding diseases with cardiovascular pathologies, elevated methylation levels of RASAL1 were observed mainly in patients who had both cardiovascular pathology and impaired renal function. The results should be validated in larger studies for confirmation due to the heterogeneous patient population. In the context of impaired renal function, RASAL1 already showed significant hypermethylation of promoter fragments and its relevance as a potential biomarker.
Keywords: RASAL1; fibrosis; DNA methylation; epigenetics; biomarker; kidney; heart
Schlagwörter: RASAL1; Fibrose; DNA Methylierung; Epigenetik; Biomarker; Niere; Herz
 
Statistik