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

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.

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.

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.

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.