Dataset Information

Gene-specific DNA methylation profiles and LINE-1 hypomethylation are associated with myocardial infarction risk.

ABSTRACT: DNA methylation profiles are responsive to environmental stimuli and metabolic shifts. This makes DNA methylation a potential biomarker of environmental-related and lifestyle-driven diseases of adulthood. Therefore, we investigated if white blood cells' (WBCs) DNA methylation profiles are associated with myocardial infarction (MI) occurrence. Whole-genome DNA methylation was investigated by microarray analysis in 292 MI cases and 292 matched controls from the large prospective Italian European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (EPICOR study). Significant signals (false discovery rate (FDR) adjusted P?

SUBMITTER: Guarrera S

PROVIDER: S-EPMC4690365 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Gene-specific DNA methylation profiles and LINE-1 hypomethylation are associated with myocardial infarction risk.

Guarrera Simonetta S Fiorito Giovanni G Onland-Moret N Charlotte NC Russo Alessia A Agnoli Claudia C Allione Alessandra A Di Gaetano Cornelia C Mattiello Amalia A Ricceri Fulvio F Chiodini Paolo P Polidoro Silvia S Frasca Graziella G Verschuren Monique W M MWM Boer Jolanda M A JMA Iacoviello Licia L van der Schouw Yvonne T YT Tumino Rosario R Vineis Paolo P Krogh Vittorio V Panico Salvatore S Sacerdote Carlotta C Matullo Giuseppe G

Clinical epigenetics 20151224

<h4>Background</h4>DNA methylation profiles are responsive to environmental stimuli and metabolic shifts. This makes DNA methylation a potential biomarker of environmental-related and lifestyle-driven diseases of adulthood. Therefore, we investigated if white blood cells' (WBCs) DNA methylation profiles are associated with myocardial infarction (MI) occurrence. Whole-genome DNA methylation was investigated by microarray analysis in 292 MI cases and 292 matched controls from the large prospective ...[more]

PMID: 26705428

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Project description:BackgroundGenetic risk scores have been developed for coronary artery disease and atherosclerosis, but are not predictive of adverse cardiovascular events. We asked whether peripheral blood expression profiles may be predictive of acute myocardial infarction (AMI) and/or cardiovascular death.MethodsPeripheral blood samples from 338 subjects aged 62 ± 11 years with coronary artery disease (CAD) were analyzed in two phases (discovery N = 175, and replication N = 163), and followed for a mean 2.4 years for cardiovascular death. Gene expression was measured on Illumina HT-12 microarrays with two different normalization procedures to control technical and biological covariates. Whole genome genotyping was used to support comparative genome-wide association studies of gene expression. Analysis of variance was combined with receiver operating curve and survival analysis to define a transcriptional signature of cardiovascular death.ResultsIn both phases, there was significant differential expression between healthy and AMI groups with overall down-regulation of genes involved in T-lymphocyte signaling and up-regulation of inflammatory genes. Expression quantitative trait loci analysis provided evidence for altered local genetic regulation of transcript abundance in AMI samples. On follow-up there were 31 cardiovascular deaths. A principal component (PC1) score capturing covariance of 238 genes that were differentially expressed between deceased and survivors in the discovery phase significantly predicted risk of cardiovascular death in the replication and combined samples (hazard ratio = 8.5, P < 0.0001) and improved the C-statistic (area under the curve 0.82 to 0.91, P = 0.03) after adjustment for traditional covariates.ConclusionsA specific blood gene expression profile is associated with a significant risk of death in Caucasian subjects with CAD. This comprises a subset of transcripts that are also altered in expression during acute myocardial infarction.

Dataset Information

Gene-specific DNA methylation profiles and LINE-1 hypomethylation are associated with myocardial infarction risk.

Publications

Gene-specific DNA methylation profiles and LINE-1 hypomethylation are associated with myocardial infarction risk.

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