Relationship between Long Interspersed Nuclear Element-1 DNA Methylation in Leukocytes and Dyslipidemia in the Japanese General Population

Aim: Aberrant global DNA methylation is involved in the development of several diseases, including cardiovascular disease (CVD). We investigated whether the methylation of long interspersed nuclear element-1 (LINE-1) in leukocytes is associated with dyslipidemia, a major risk factor for CVD, in the Japanese general population. Methods: We conducted a cross-sectional study consisting of 420 Japanese subjects (187 men and 233 women) without a clinical history of cancer, stroke, or ischemic heart disease. LINE-1 DNA methylation levels in leukocytes were measured using a pyrosequencing method. Results: Significantly higher odds ratios (ORs) for hypermethylation were observed in the high LDL cholesterol and high LDL/HDL ratio groups than the corresponding normal group (high LDLC group: OR, 1.88; 95% confidence interval [CI], 1.20–2.96, high LDL/HDL ratio group: OR, 1.90; 95% CI, 1.20–3.01). Subjects with 2 or more lipid abnormalities had significantly higher ORs for hypermethylation than those with no lipid abnormality (OR, 2.31; 95% CI, 1.11–4.82). Conclusion: LINE-1 DNA hypermethylation in leukocytes was associated with CVD risk profiles: high LDLC, high LDL/HDL ratio, and the degree of abnormal lipid metabolism. Abbreviations:ANOVA, analysis of variance; BMI, body mass index; CI, confidence interval; CRP, C-reactive protein; CVD, cardiovascular disease; DNMT, DNA methyltransferase; EDTA, ethylenediaminetetraacetic acid; HDLC, high-density lipoprotein cholesterol; IL-6, interleukin-6; KLF2, Krüppel-like factor 2; LDLC, low-density lipoprotein cholesterol; LINE-1, long interspersed nuclear element-1; OR, odds ratio; PCR, polymerase chain reaction; SD, standard deviation; TC, total cholesterol; TG, triglyceride;