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, Silvia Polidoro, Graziella Frasca, Monique W M Verschuren, Jolanda M A Boer, Licia Iacoviello, Yvonne T. van der Schouw, Rosario Tumino, Paolo Vineis, Vittorio Krogh, Salvatore PanicoCarlotta Sacerdote, Giuseppe Matullo

Research output: Contribution to journalArticle

Abstract

Background: 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. Results: A 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). Conclusions: Our 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.

Original languageEnglish
JournalClinical Epigenetics
DOIs
Publication statusAccepted/In press - Dec 24 2015

Keywords

  • Association study
  • DNA methylation
  • Early biomarkers
  • Myocardial infarction
  • Risk prediction
  • Risk stratification

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Developmental Biology
  • Genetics(clinical)

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    Guarrera, S., Fiorito, G., Onland-Moret, N. C., Russo, A., Agnoli, C., Allione, A., Di Gaetano, C., Mattiello, A., Ricceri, F., Chiodini, P., Polidoro, S., Frasca, G., Verschuren, M. W. M., Boer, J. M. A., Iacoviello, L., van der Schouw, Y. T., Tumino, R., Vineis, P., Krogh, V., ... Matullo, G. (Accepted/In press). Gene-specific DNA methylation profiles and LINE-1 hypomethylation are associated with myocardial infarction risk. Clinical Epigenetics. https://doi.org/10.1186/s13148-015-0164-3