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Identification of differentially methylated BRCA1 and CRISP2 DNA regions as blood surrogate markers for cardiovascular disease

Istas, Geoffrey, Declerck, Ken, Pudenz, Maria, Szic, Katarzyna Szarc vel, Lendinez-Tortajada, Veronica, Leon-Latre, Montserrat, Heyninck, Karen, Haegeman, Guy, Casasnovas, Jose A., Tellez-Plaza, Maria , Gerhauser, Clarissa, Heiss, Christian, Rodriguez-Mateos, Ana and Berghe, Wim Vanden (2017) Identification of differentially methylated BRCA1 and CRISP2 DNA regions as blood surrogate markers for cardiovascular disease Scientific Reports, 7, 5120.

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Abstract

Genome-wide Illumina InfiniumMethylation 450 K DNA methylation analysis was performed on blood samples from clinical atherosclerosis patients (n = 8) and healthy donors (n = 8) in the LVAD study (NCT02174133, NCT01799005). Multiple differentially methylated regions (DMR) could be identified in atherosclerosis patients, related to epigenetic control of cell adhesion, chemotaxis, cytoskeletal reorganisations, cell proliferation, cell death, estrogen receptor pathways and phagocytic immune responses. Furthermore, a subset of 34 DMRs related to impaired oxidative stress, DNA repair, and inflammatory pathways could be replicated in an independent cohort study of donor-matched healthy and atherosclerotic human aorta tissue (n = 15) and human carotid plaque samples (n = 19). Upon integrated network analysis, BRCA1 and CRISP2 DMRs were identified as most central disease-associated DNA methylation biomarkers. Differentially methylated BRCA1 and CRISP2 regions were verified by MassARRAY Epityper and pyrosequencing assays and could be further replicated in blood, aorta tissue and carotid plaque material of atherosclerosis patients. Moreover, methylation changes at BRCA1 and CRISP2 specific CpG sites were consistently associated with subclinical atherosclerosis measures (coronary calcium score and carotid intima media thickness) in an independent sample cohort of middle-aged men with subclinical cardiovascular disease in the Aragon Workers’ Health Study (n = 24). Altogether, BRCA1 and CRISP2 DMRs hold promise as novel blood surrogate markers for early risk stratification and CVD prevention.

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine
Authors :
NameEmailORCID
Istas, Geoffrey
Declerck, Ken
Pudenz, Maria
Szic, Katarzyna Szarc vel
Lendinez-Tortajada, Veronica
Leon-Latre, Montserrat
Heyninck, Karen
Haegeman, Guy
Casasnovas, Jose A.
Tellez-Plaza, Maria
Gerhauser, Clarissa
Heiss, Christianc.heiss@surrey.ac.uk
Rodriguez-Mateos, Ana
Berghe, Wim Vanden
Date : 11 July 2017
DOI : 10.1038/s41598-017-03434-0
Depositing User : Melanie Hughes
Date Deposited : 16 Aug 2018 14:01
Last Modified : 16 Aug 2018 14:01
URI: http://epubs.surrey.ac.uk/id/eprint/848988

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