DNA methylation signatures of tobacco smoking in a high cardiovascular risk population: modulation by the mediterranean diet

Authors: FERNANDEZ-CARRION, REBECA - Instituto De Salud Carlos Iii; SORLI, JOSE - Instituto De Salud Carlos Iii; ASENSIO, EVA - University Of Valencia; PASCUAL, EVA - University Of Valencia; PORTOLES, OLGA - University Of Valencia; ALVAREZ SALA, ANDREA - University Of Valencia; FRANCES, FRANCESC - University Of Valencia; RAMIREZ SABIO, JUDITH - Sagunto Hospital; PEREZ FIDALGO, ALEHANDRO - University Clinical Hospital Of Valencia; VILLAMIL, LAURA - University Antonio Narino; TINAHONES, FRANCISCO - University Of Malaga; ESTRUCH, RAMON - University Of Barcelona; ORDOVAS, JOSE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; COLTELL, OSCAR - Jaume I University; CORELLA, DOLORES - University Of Valencia

Submitted to: International Journal of Environmental Research and Public Health
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/16/2023
Publication Date: 2/18/2023
Citation: Fernandez-Carrion, R., Sorli, J.V., Asensio, E.M., Pascual, E.C., Portoles, O., Alvarez Sala, A., Frances, F., Ramirez Sabio, J.B., Perez Fidalgo, A., Villamil, L., Tinahones, F.J., Estruch, R., Ordovas, J.M., Coltell, O., Corella, D. 2023. DNA methylation signatures of tobacco smoking in a high cardiovascular risk population: modulation by the mediterranean diet. International Journal of Environmental Research and Public Health. https://doi.org/10.3390/ijerph20043635.
DOI: https://doi.org/10.3390/ijerph20043635

Interpretive Summary: Scientists have been studying how our lifestyle choices, like smoking and diet, can affect our health at the DNA methylation (epigenetics) level. This research revealed significant findings regarding the impact of smoking on DNA methylation in a group of 414 people at high risk of heart disease from the Mediterranean region. We identified changes in the DNA that could potentially be used as markers to monitor health status or risk. In addition to these findings, the research also revealed some interesting findings about the Mediterranean diet. It appears that adhering to this diet could influence the DNA methylation changes caused by smoking. The research suggests that our lifestyle choices not only affect our health directly, but also indirectly by influencing how our body's DNA methylation responds to harmful substances like tobacco.

Technical 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 x 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.