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

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.

Methylation in cornea and corneal diseases: a systematic review

“…The methylation process can be influenced by various factors, including genetics, individual characteristics, and environmental influences such as aflatoxin B1 and air pollution. While genetic factors are known to affect susceptibility, non-genetic risk factors like DNA methylation modifications, histone modifications, and inflammatory risk factors are also gaining attention in this regard [144][145][146][147]. Methylation levels in tissues are variable and dynamic [148,149], with a balance between establishing and eliminating methylation [33], which is mediated by methyltransferases and demethylases [150] (Fig.…”

From multi-omics approaches to personalized medicine in myocardial infarction

“…Nicotinamide mononucleotide could enhance Notch1 expression, leading to improved cardiomyocyte survival and cardiac function ( 74 ). Furthermore, lifestyle factors, such as diet, exercise, and smoking cessation, have been demonstrated to influence DNA methylation ( 75 – 77 ). Maintaining a healthy lifestyle during MI recovery can potentially enhance cardiovascular health by impacting DNA methylation.…”

Associations between the New DNA-Methylation-Based Telomere Length Estimator, the Mediterranean Diet and Genetics in a Spanish Population at High Cardiovascular Risk

“…In addition, we assessed the complete blood count (CBC) in peripheral blood samples. The CBC included the total number of leukocytes as well as the type of white blood cells (neutrophils, eosinophils, basophils, monocytes, and lymphocytes) as previously indicated [92]. Blood pressure was measured by qualified personnel using the study protocol and a validated semiautomatic oscillometer (Omron HEM-705CP, Hoofddorp, The Netherlands) [88].…”

“…The greater the score (0 to 17), the greater the adherence to the MedDiet pattern. As previously reported [92], the overall score was categorized into two groups representing low (from 0 to 8 points) and high (from 9 to 17 points) adherence to the MedDiet. Both the overall score and specific food items were analyzed.…”

“…At baseline, DNA was extracted from as described in a prior publication [92]. Doublestranded DNA was quantified using PicoGreen (Invitrogen Corporation, Carlsbad, CA, USA).…”