Evidence map›Paper›PMID 26705428›Full record

ArticleClinical epigenetics2015

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

Simonetta Guarrera, Giovanni Fiorito, N Charlotte Onland-Moret, Alessia Russo, Claudia Agnoli, Alessandra Allione, Cornelia Di Gaetano, Amalia Mattiello, Fulvio Ricceri, Paolo Chiodini and 12 more

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In one paragraph

Article in Clinical epigenetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed, 3 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

49 citing papers in PubMed, 3 syntheses or guidelines pooled it.

  1. Pooled it
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  3. Promoter Polymorphism (-174, G/C) of Interleukin-6 and Arterial Thromboembolic Events: A Meta-Analysis.Medical science monitor : international medical journal of experimental and clinical research · 2016
    Pooled it
  4. Effects of Physical Exercise on Endothelial Function and DNA Methylation.International journal of environmental research and public health · 2019
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

22 authors.

Simonetta Guarrera *Human Genetics Foundation (HuGeF), Via Nizza 52, Turin, I-10126 Torino Italy.
Giovanni Fiorito *Human Genetics Foundation (HuGeF), Via Nizza 52, Turin, I-10126 Torino Italy.
N Charlotte Onland-MoretJulius Center for Health Sciences and Primary Care, UMC Utrecht, Utrecht, The Netherlands.
Alessia RussoHuman Genetics Foundation (HuGeF), Via Nizza 52, Turin, I-10126 Torino Italy.
Claudia AgnoliEpidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
Alessandra AllioneHuman Genetics Foundation (HuGeF), Via Nizza 52, Turin, I-10126 Torino Italy.
Cornelia Di GaetanoHuman Genetics Foundation (HuGeF), Via Nizza 52, Turin, I-10126 Torino Italy.
Amalia MattielloDepartment of Clinical and Experimental Medicine, Federico II University, Naples, Italy.
Fulvio RicceriCancer Epidemiology, CPO Piemonte, Turin, Italy.
Paolo ChiodiniDepartment of Public Health, Second University of Naples, Naples, Italy.
Silvia PolidoroHuman Genetics Foundation (HuGeF), Via Nizza 52, Turin, I-10126 Torino Italy.
Graziella FrascaCancer Registry and Histopathology Unit, "Civile-M.P. Arezzo" Hospital, ASP 7, Ragusa, Italy.
Monique W M VerschurenJulius Center for Health Sciences and Primary Care, UMC Utrecht, Utrecht, The Netherlands.
Jolanda M A BoerCentre for Nutrition, Prevention and Health Services, National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
Licia IacovielloDepartment of Epidemiology and Prevention, IRCCS Istituto Neurologico Mediterraneo Neuromed, Pozzilli, IS Italy.
Yvonne T van der SchouwJulius Center for Health Sciences and Primary Care, UMC Utrecht, Utrecht, The Netherlands.
Rosario TuminoCancer Registry and Histopathology Unit, "Civile-M.P. Arezzo" Hospital, ASP 7, Ragusa, Italy.
Paolo VineisHuman Genetics Foundation (HuGeF), Via Nizza 52, Turin, I-10126 Torino Italy.
Vittorio KroghEpidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
Salvatore PanicoDepartment of Clinical and Experimental Medicine, Federico II University, Naples, Italy.
Carlotta SacerdoteCancer Epidemiology, CPO Piemonte, Turin, Italy.
Giuseppe MatulloHuman Genetics Foundation (HuGeF), Via Nizza 52, Turin, I-10126 Torino Italy.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundDNA 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 < 0.05) were replicated by mass spectrometry in 317 MI cases and 262 controls from the Dutch EPIC cohort (EPIC-NL). Long interspersed nuclear element-1 (LINE-1) methylation profiles were also evaluated in both groups.

resultsA differentially methylated region (DMR) within the zinc finger and BTB domain-containing protein 12 (ZBTB12) gene body and LINE-1 hypomethylation were identified in EPICOR MI cases and replicated in the EPIC-NL sample (ZBTB12-DMR meta-analysis: effect size ± se = -0.016 ± 0.003, 95 % CI = -0.021;-0.011, P = 7.54 × 10(-10); LINE-1 methylation meta-analysis: effect size ± se = -0.161 ± 0.040, 95 % CI = -0.239;-0.082, P = 6.01 × 10(-5)). Moreover, cases with shorter time to disease had more pronounced ZBTB12-DMR hypomethylation (meta-analysis, men: effect size ± se = -0.0059 ± 0.0017, P TREND = 5.0 × 10(-4); women: effect size ± se = -0.0053 ± 0.0019, P TREND = 6.5 × 10(-3)) and LINE-1 hypomethylation (meta-analysis, men: effect size ± se = -0.0010 ± 0.0003, P TREND = 1.6 × 10(-3); women: effect size ± se = -0.0008 ± 0.0004, P TREND = 0.026) than MI cases with longer time to disease. In the EPIC-NL replication panel, DNA methylation profiles improved case-control discrimination and reclassification when compared with traditional MI risk factors only (net reclassification improvement (95 % CI) between 0.23 (0.02-0.43), P = 0.034, and 0.89 (0.64-1.14), P < 1 × 10(-5)).

conclusionsOur data suggest that specific methylation profiles can be detected in WBCs, in a preclinical condition, several years before the occurrence of MI, providing an independent signature of cardiovascular risk. We showed that prediction accuracy can be improved when DNA methylation is taken into account together with traditional MI risk factors, although further confirmation on a larger sample is warranted. Our findings support the potential use of DNA methylation patterns in peripheral blood white cells as promising early biomarkers of MI.

Indexed as

Association studyDNA methylationEarly biomarkersMyocardial infarctionRisk predictionRisk stratification

Identifiers

PMID26705428
PMCPMC4690365

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.