DNA-Methylation Signatures of Tobacco Smoking in a High Cardiovascular Risk Population: Modulation by the Mediterranean Diet

Rebeca Fernández-Carrión, José V. Sorlí, Eva M. Asensio, Eva C. Pascual, Olga Portolés, Andrea Alvarez-Sala, Francesc Francès, Judith B. Ramírez-Sabio, Alejandro Pérez-Fidalgo, Laura V. Villamil, Francisco J. Tinahones, Ramon Estruch, Jose M. Ordovas, Oscar Coltell and Dolores Corella ()
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Rebeca Fernández-Carrión: Department of Preventive Medicine and Public Health, School of Medicine, University of Valencia, 46010 Valencia, Spain
José V. Sorlí: Department of Preventive Medicine and Public Health, School of Medicine, University of Valencia, 46010 Valencia, Spain
Eva M. Asensio: Department of Preventive Medicine and Public Health, School of Medicine, University of Valencia, 46010 Valencia, Spain
Eva C. Pascual: Department of Preventive Medicine and Public Health, School of Medicine, University of Valencia, 46010 Valencia, Spain
Olga Portolés: Department of Preventive Medicine and Public Health, School of Medicine, University of Valencia, 46010 Valencia, Spain
Andrea Alvarez-Sala: Department of Preventive Medicine and Public Health, School of Medicine, University of Valencia, 46010 Valencia, Spain
Francesc Francès: Department of Preventive Medicine and Public Health, School of Medicine, University of Valencia, 46010 Valencia, Spain
Judith B. Ramírez-Sabio: Oncology Service, Sagunto Hospital, 46520 Valencia, Spain
Alejandro Pérez-Fidalgo: Department of Medical Oncology, University Clinic Hospital of Valencia, 46010 Valencia, Spain
Laura V. Villamil: Department of Physiology, School of Medicine, University Antonio Nariño, Bogotá 111511, Colombia
Francisco J. Tinahones: CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, 28029 Madrid, Spain
Ramon Estruch: CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, 28029 Madrid, Spain
Jose M. Ordovas: CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, 28029 Madrid, Spain
Oscar Coltell: CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, 28029 Madrid, Spain
Dolores Corella: Department of Preventive Medicine and Public Health, School of Medicine, University of Valencia, 46010 Valencia, Spain

IJERPH, 2023, vol. 20, issue 4, 1-26

Abstract: Biomarkers based on DNA methylation are relevant in the field of environmental health for precision health. Although tobacco smoking is one of the factors with a strong and consistent impact on DNA methylation, there are very few studies analyzing its methylation signature in southern European populations and none examining its modulation by the Mediterranean diet at the epigenome-wide level. We examined blood methylation smoking signatures on the EPIC 850 K array in this population (n = 414 high cardiovascular risk subjects). Epigenome-wide methylation studies (EWASs) were performed analyzing differential methylation CpG sites by smoking status (never, former, and current smokers) and the modulation by adherence to a Mediterranean diet score was explored. Gene-set enrichment analysis was performed for biological and functional interpretation. The predictive value of the top differentially methylated CpGs was analyzed using receiver operative curves. We characterized the DNA methylation signature of smoking in this Mediterranean population by identifying 46 differentially methylated CpGs at the EWAS level in the whole population. The strongest association was observed at the cg21566642 ( p = 2.2 × 10 −32 ) in the 2q37.1 region. We also detected other CpGs that have been consistently reported in prior research and discovered some novel differentially methylated CpG sites in subgroup analyses. In addition, we found distinct methylation profiles based on the adherence to the Mediterranean diet. Particularly, we obtained a significant interaction between smoking and diet modulating the cg5575921 methylation in the AHRR gene. In conclusion, we have characterized biomarkers of the methylation signature of tobacco smoking in this population, and suggest that the Mediterranean diet can increase methylation of certain hypomethylated sites.

Keywords: DNA methylation; tobacco smoking; EWAS; Mediterranean diet; precision health; epigenetic biomarkers; dietary modulation (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2023
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