Assessment of global long interspersed nucleotide element‐1 (LINE‐1) DNA methylation in a longitudinal cohort of type 2 diabetes mellitus (T2DM) individuals

Introduction Recent studies have indicated that methylation of the LINE‐1 elements is associated with an increased risk of worsening carbohydrate metabolism. It has been shown that overall DNA methylation of LINE‐1 elements could be considered as a risk factor for T2DM and its complications, independent of other established risk factors. Methods A total of 794 T2DM individuals from Salford, UK were included in this study (60% men n = 470). All patients had clinical and metabolic variables measured in 2002 (baseline outcomes) and annually through to 2016. Global LINE‐1 DNA methylation was measured at four CpG sites. The QIAGEN PyroMark Q96 MD pyrosequencer was used to quantify methylation. Results The overall mean ± SD global LINE‐1 methylation was 75.81 ± 3.25%. Cross‐sectional linear regression analysis at baseline year 2002 showed that LINE‐1 methylation was a significant predictor of diastolic BP (adjusted beta coefficient β = −0.25), estimated glomerular filtration rate (eGFR) (β = −0.48) and cholesterol HDL ratio (β = −0.04). A 10% increase in LINE‐1 methylation was associated with a lower diastolic BP by 2.5 mm Hg, a lower eGFR by 4.8 ml/min/1.73 m2 and decreased cholesterol/HDL ratio by 0.4 mmol/L. Longitudinal analysis over the 14‐year‐follow‐up periods showed that global LINE‐1 methylation at baseline was associated with lower BMI in women [β = −0.25] and lower cholesterol: HDL ratio [β = −0.07]. A 10% increase in LINE‐1 methylation was associated with reduction in BMI by 2.5 kg/m2 in women and reduction in cholesterol:HDL ratio by 0.7 mmol/L. Conclusion In a 14‐year longitudinal cohort of T2DM individuals, relations between global LINE‐1 DNA methylation status and specific metabolic markers were seen. Also, a higher degree of DNA methylation was predictive of less weight gain over time in women.