Record #342533 - GSI Repository

U-BiomarCARE

Moving from whole genome cfDNA methylation to a PCR-based liquid biopsy assay for detecting high-risk atherosclerotic plaques

Grant period	2023-07-01 - 2024-12-31
Funding body	European Union
Call number	ERC-2023-POC
Grant number	101123220
Identifier	G:(EU-Grant)101123220

Note: General practitioners and cardiologists are faced every day with challenging decisions on whom to refer for diagnostics of coronary artery disease (CAD) as sign and symptoms of cardiac ischemia require immediate action. Diagnosis of CAD is key as ischemic heart disease accounts for 45% of deaths in females and 39% in males in the European Union. Yet, diagnosis of CAD in women is regularly delayed and often unrecognized. As the main pathology underlying CAD, it is essential to understand atherosclerotic plaque biology. In recent years, my research group and others have identified clear sex differences in the atherosclerotic plaque morphology and its (epi)genetic regulation. One consequence is that female plaques are more difficult to detect than male plaques, especially those which cause symptoms. As part of the ERC UCARE project, we uncovered a plaque-specific epigenetic signal in cell-free DNA from plasma of women with CAD. This signal consisted of hypomethylated regions specific for plaques that can be detected in plasma cell-free DNA. Our methods thus far have been focused on whole genome sequencing analyses. Yet, for studying the predictive value of these regions in large cohorts of patients with CAD, as well as exploring commercial potential, we need to develop a more specific methodology. Our aim in this current U-BiomarCARE project is to investigate if the methylation status of plaque-specific regions can be detected in plasma with a PCR-based method. Once we prove that this methodology is reproducible and comparable to whole genome DNA methylation sequencing, we can perform large biomarker studies in both women and men suspected of heart disease and explore potential commercialization of plaque-specific cell-free DNA methylation profiles to accurately detect CAD. This will be a game changer for the healthcare sector as it will allow a specific and timely detection of dangerous atherosclerotic plaques both in men and women.

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Record created 2023-08-27, last modified 2023-08-27

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