DNA methylation as a biomarker for cardiometabolic disease risk

Abstract Funding Acknowledgements Type of funding sources: None. Cardiovascular disease (CVD) is the leading cause of death in most countries [1]. Risk factors known to predispose to the development of CVD include increasing age, male gender, diabetes mellitus, high blood cholesterol, tobacco smoking, high blood pressure (hypertension), obesity, physical inactivity, and family history [2]. Elevated plasma homocysteine is also an independent risk factor for CVD [2,3]. The mechanism by which elevated homocysteine contributes to CVD risk is not well understood, but it is well-established that dietary folate and vitamin B supplementation can reduce serum homocysteine levels by facilitating remethylation of homocysteine to methionine [4]. DNA methylation can modulate gene expression in response to exposure to various substances, such as nutrients, smoking, and environmental chemicals.Variation in healthy aging and lifespan is ascribed more to various non-genetic factors than to inherited genetic determinants, and a major goal in aging research is to reveal the epigenetic basis of aging. The remethylation cycle is essential for the systemic methyl donor supply, which is used for important biological processes, such as cytosine-5 methylation of genomic DNA, an epigenetic modification that plays an important role in maintaining genomic stability, chromatin structure, and in controlling transcriptional capacity [2,4]. Methodology/Principal Findings In this prospective study, we examined both gender patients, aged 40-50 years. Relationship between prevalence of Cardiometabolic risk factors (metabolic syndrome, oxidative stress and arterial hypertension) or its predisposing conditions (hypertrigliceridemia, dislipedimia, inusline resistance, D vitamin hipovitaminosis)) and DNA hydroximethylation was investigated. Hydroxymethylation measurement was done using a gold standard technique (liquid chromatography + mass spectrometry), the biological age equivalent was calculated by LC-MS in laboratories Reunis, to verify the potential value of DNA methylation as a CVD biomarker. Results Generally, 296 both gender patients were analyzed regarding metabolic syndrome and oxidative stress, age group 40-50 years (Me=47,1). MethylAge (DNA-hydroxymethylation) in analyzed group has average age 40,1 years old. DNA Hydroxymethylation is higher in those individuals, who has increased waist circumference, as well as, statistically significant correlation was observed between MethylAge waist circumference, metabolic syndrome and hypertriglyceridemia (p<0,05). Conclusion The evidence that the age-related changes in DNA methylation play a role in aging comes from studies of anti-aging interventions (e.g., caloric restriction, iron deficiency, dyslipidemia). Our data showed a link between premature biological ageing and waist circumference, hypertrigliceridimia. Hydroxymethylation of DNA is a good epigenetic marker for aging and risk assessment, especially in alliance with AGEs and oxidative stress research.