Impact of inflammation on epigenetic DNA methylation – a novel risk factor for cardiovascular disease?

Abstract

Objective. The lifespan of dialysis patients is as short as in patients with metastatic cancer disease, mainly due to cardiovascular disease (CVD). DNA methylation is an important cellular mechanism modulating gene expression associated with ageing, inflammation and atherosclerotic processes.Design. DNA methylation was analysed in peripheral blood leucocytes from three different groups of chronic kidney disease (CKD) populations (37 CKD stages 3 and 4 patients, 98 CKD stage 5 patients and 20 prevalent haemodialysis patients). Thirty-six healthy subjects served as controls. Clinical characteristics (diabetes mellitus, nutritional status and presence of clinical CVD), inflammation and oxidative stress biomarkers, homocysteine and global DNA methylation in peripheral blood leucocytes (defined as HpaII/ MspI ratio by the Luminometric Methylation Assay method) were evaluated. CKD stage 5 patients (n ¼ 98) starting dialysis treatment were followed for a period of 36 ± 2 months.Results. Inflamed patients had lower ratios of HpaII/ MspI, indicating global DNA hypermethylation. Analysis by the Cox regression model demonstrated that DNA hypermethylation (HpaII/MspI ratio <median) was significantly associated with both all-cause (RR 5.0; 95% CI: 1.7-14.8; P < 0.01) and cardiovascular (RR 13.9; 95% CI: 1.8-109.3; P < 0.05) mortality, even following the adjustment for age, CVD, diabetes mellitus and inflammation.Conclusion. The present study demonstrates that global DNA hypermethylation is associated with inflammation and increased mortality in CKD.

Emerging Biomarkers for Evaluating Cardiovascular Risk in the Chronic Kidney Disease Patient

“…Hodge et al (197) have demonstrated that the inflammatory cytokine IL-6 might exert an impact on epigenetic changes in cells via regulation of a DNA methyltransferase gene. In accordance, we demonstrated that global DNA hypermethylation was associated with inflammation and increased mortality in CKD (198). As we also find Figure 4.…”

Leptin and TNF-alpha promoter methylation levels measured by MSP could predict the response to a low-calorie diet

“…There are dynamic changes in the DNA methylation pattern during the lifetime and several environmental factors such as dietary compounds [12], oxidative stress [15], hypoxia [36], inflammation [37] or ageing [35] may affect methylation status and modify gene expression. Thus, changes in the DNA methylation pattern as a result of dietary treatments or conditions have been studied in the last years, comparing vegetarians with omnivores [39], the effects of different obesogenic diets [26,31] or different dietary treatments to lose weight [7].…”

Significant differences in global genomic DNA methylation by gender and race/ethnicity in peripheral blood

“…Recent studies also indicated a good correlation between levels of leukocyte DNA methylation and degrees of inflammation, suggesting DNA methylation may represent a novel pathway underlying the association between obesity, inflammation and cancer risk. 19,20 Although BMI is the most commonly used measure for obesity, it does not adequately capture body fat mass and the distribution of body fat. We characterized body composition using % body fat and areas of subcutaneous fat (SAT) and visceral fat (VAT) (cm 2 ).…”