Global LINE-1 DNA methylation is associated with blood glycaemic and lipid profiles

Abstract

Background Patterns of DNA methylation change with age and these changes are believed to be associated with the development of common complex diseases. The hypothesis that Long Interspersed Nucleotide Element 1 (LINE-1) DNA methylation (an index of global DNA methylation) is associated with biomarkers of metabolic health was investigated in this study. Methods Global LINE-1 DNA methylation was quantified by pyrosequencing in blood-derived DNA samples from 228 individuals, aged 49–51 years, from the Newcastle Thousand Families Study (NTFS). Associations between log-transformed LINE-1 DNA methylation levels and anthropometric and blood biochemical measurements, including triglycerides, total cholesterol, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, fasting glucose and insulin secretion and resistance were examined. Results Linear regression, after adjustment for sex, demonstrated positive associations between log-transformed LINE-1 DNA methylation and fasting glucose {coefficient 2.80 [95% confidence interval (CI) 0.39–5.22]}, total cholesterol [4.76 (95% CI 1.43–8.10)], triglycerides [3.83 (95% CI 1.30–6.37)] and LDL-cholesterol [5.38 (95% CI 2.12–8.64)] concentrations. A negative association was observed between log-transformed LINE-1 methylation and both HDL cholesterol concentration [−1.43 (95% CI −2.38 to −0.48)] and HDL:LDL ratio [−1.06 (95% CI −1.76 to −0.36)]. These coefficients reflect the millimoles per litre change in biochemical measurements per unit increase in log-transformed LINE-1 methylation. Conclusions These novel associations between global LINE-1 DNA methylation and blood glycaemic and lipid profiles highlight a potential role for epigenetic biomarkers as predictors of metabolic disease and may be relevant to future diagnosis, prevention and treatment of this group of disorders. Further work is required to establish the role of confounding and reverse causation in the observed associations.

DNA Methylation and Hydroxymethylation Levels in Relation to Two Weight Loss Strategies: Energy-Restricted Diet or Bariatric Surgery

“…However, other studies have suggested that DNA methylation may be related to weight status [19,40]. On the other hand, the current study found an association between serum glucose levels and LINE-1 methylation, supporting data from others trials [39,41]. In this sense, increased DNA methylation levels have been reported in individuals with higher blood glucose levels [42].…”

Metabolic, hormonal and immunological associations with global DNA methylation among postmenopausal women

“…This is similar to what has been recently reported. 41 Pearce and colleagues reported that a 10% increase in LINE-1 methylation was associated with an 0.28 mmol/l increase in fasting glucose concentrations. 41 Furthermore, global DNA methylation has also been shown to be associated with insulin resistance with a 10% increase in global DNA methylation resulting from a 4.55 unit increase in homeostasis model assessment.…”

“…41 Pearce and colleagues reported that a 10% increase in LINE-1 methylation was associated with an 0.28 mmol/l increase in fasting glucose concentrations. 41 Furthermore, global DNA methylation has also been shown to be associated with insulin resistance with a 10% increase in global DNA methylation resulting from a 4.55 unit increase in homeostasis model assessment. 42 A potential biological mechanism linking promoter-specific hypermethylation to several sex hormones among women with low serum folate levels and those who did not use multivitamins, but not among women with high folate levels and those who used multivitamins.…”

Diet-induced (epigenetic) changes in bone marrow augment atherosclerosis

“…This suggests that hypercholesterolemia might form a link between altered DNA methylation patterning in blood leukocytes and increased susceptibility to atherosclerotic lesion development. In line, a study by Pearce et al [19] demonstrated that human blood lipid profiles positively correlate with global DNA methylation, measured as LINE methylation. Interestingly, HDL cholesterol levels are negatively correlated with LINE methylation, whereas LDL cholesterol shows a strong, positive correlation.…”