Metabolic syndrome components are associated with DNA hypomethylation

Abstract

Disturbances of DNA methylation have been associated with multiple diseases, including cardiovascular disease, cancer and, as some have suggested, glucometabolic disturbances. Our aim was to assess the association of the metabolic syndrome and its individual components with DNA methylation in a population-based study. In a human population (n = 738) stratified by age, sex and glucose metabolism, we explored associations of the metabolic syndrome according to National Cholesterol Education Program/Adult Treatment Panel-III criteria and its individual components (fasting glucose, high-density lipoprotein cholesterol, triglycerides, blood pressure, waist circumference) with global leukocyte DNA methylation. DNA methylation was measured as the methylcytosine/cytosine ratio in peripheral leukocytes using liquid chromatography-tandem mass spectrometry. Individuals with the metabolic syndrome had relative DNA hypomethylation compared to participants without the syndrome (β = -0.05; p = 0.01). This association was mainly attributable to linear associations of two metabolic syndrome components with DNA methylation: fasting plasma glucose (β = -0.02; p = 0.004) and high-density lipoprotein cholesterol (β = 0.07; p = 0.004). People with type 2 diabetes or impaired glucose metabolism had DNA hypomethylation compared to normoglycemic individuals (β = -0.05; p = 0.004). DNA hypomethylation is independently associated with hyperglycemia and low high-density lipoprotein cholesterol, both essential components of the metabolic syndrome. The potential implications and direction of possible causality require further study.