Epigenome-wide association study reveals differential DNA methylation in individuals with a history of myocardial infarction.
Cardiovascular diseases (CVDs) are the leading causes of death worldwide and represent a substantial economic burden on public health care systems. Epigenetic markers have potential as diagnostic markers before clinical symptoms have emerged, and as prognostic markers to inform the choice of clinical intervention. In this study, we performed an epigenome-wide association study (EWAS) for CVDs, to identify disease-specific alterations in DNA methylation. CpG methylation in blood samples from the northern Sweden population health study (NSPHS) (n = 729) was assayed on the Illumina Infinium HumanMethylation450 BeadChip. Individuals with a history of a CVD were identified in the cohort. It included individuals with hypertension (N = 147), myocardial infarction (MI) (N = 48), stroke (N = 27), thrombosis (N = 22) and cardiac arrhythmia (N = 5). Differential DNA methylation was observed at 211 CpG-sites in individuals with a history of MI (q <0.05). These sites represent 196 genes, of which 42 have been described in the scientific literature to be related to cardiac function, cardiovascular disease, cardiogenesis and recovery after ischemic injury. We have shown that individuals with a history of MI have a deviating pattern of DNA methylation at many genomic loci of which a large fraction has previously been linked to CVD. Our results highlight genes that might be important in the pathogenesis of MI or in recovery. In addition, the sites pointed out in this study can serve as candidates for further evaluation as potential biomarkers for MI.
Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
Mathias
M
Rask-Andersen
Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
David
D
Martinsson
Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
Muhammad
M
Ahsan
Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
Stefan
S
Enroth
Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
Weronica E
WE
Ek
Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
Ulf
U
Gyllensten
Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
Åsa
Å
Johansson
D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000235:genetics*; D015331:Cohort Studies; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics; D044127:Epigenesis, Genetic / Q000235:genetics; D057890:Epigenomics / Q000379:methods; D005260:Female; D015894:Genome, Human / Q000235:genetics; D055106:Genome-Wide Association Study; D006801:Humans; D006973:Hypertension / Q000235:genetics; D008297:Male; D009203:Myocardial Infarction / Q000097:blood / Q000235:genetics*; D013548:Sweden
D015415:Biomarkers