Association between global leukocyte DNA methylation and cardiovascular risk in postmenopausal women

Abstract

BackgroundGenetic studies to date have not provided satisfactory evidence regarding risk polymorphisms for cardiovascular disease (CVD). Conversely, epigenetic mechanisms, including DNA methylation, seem to influence the risk of CVD and related conditions. Because postmenopausal women experience an increase in CVD, we set out to determine whether global DNA methylation was associated with cardiovascular risk in this population.MethodsIn this cross sectional study carried out in a university hospital, 90 postmenopausal women without prior CVD diagnosis (55.5 ± 4.9 years, 5.8 [3.0–10.0] years since menopause) were enrolled. DNA was extracted from peripheral leukocytes and global DNA methylation levels were obtained with an ELISA kit. Cardiovascular risk was estimated by the Framingham General Cardiovascular Risk Score (10-year risk) (FRS). Clinical and laboratory variables were assessed. Patients were stratified into two CVD risk groups: low (FRS: <10 %, n = 69) and intermediate/high risk (FRS ≥10 %, n = 21).ResultsAge, time since menopause, blood pressure, total cholesterol, and LDL-c levels were higher in FRS ≥10 % group vs. FRS <10 % group. BMI, triglycerides, HDL-c, HOMA-IR, glucose and hsC-reactive protein levels were similar in the two groups. Global DNA methylation (% 5mC) in the overall sample was 26.5 % (23.6–36.9). The FRS ≥10 % group presented lower global methylation levels compared with the FRS <10 % group: 23.9 % (20.6–29.1) vs. 28.8 % (24.3–39.6), p = 0.02. This analysis remained significant even after adjustment for time since menopause (p = 0.02).ConclusionsOur results indicate that lower global DNA methylation is associated with higher cardiovascular risk in postmenopausal women.

Association between DNA methylation and coronary heart disease or other atherosclerotic events: A systematic review

“…In total, 51 articles met our eligibility criteria (Supplementary Table 1) and were included in the analysis. Of the 51 selected studies, 17 included participants from Europe [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] 14 from China [23][24][25][26][27][28][29][30][31][32][33][34][35][36], six from USA [37][38][39][40][41][42], three from India [43][44][45], two from Canada [46,47], and one each from Japan [48], Malaysia [49], Iran [50], Russia [51], Brazil [52] and Mexico [53]…”

“…Seven studies analyzed global DNA methylation [6,7,23,34,36,42,52], 31 followed a candidate-gene approach [8][9][10][11][12][13][14]20,22,[24][25][26][27][28][29][30][31][32][33]35,[38][39][40][41]45,46,49,50,[54][55][56], seven were epigenome-wide association studies (EWAS) [16,18,19,21,44,48,53], two used both global DNA methylation and candidate-gene approaches [37,43], three used EWAS and global DNA methylation approaches [15,17,51], and on...…”

CBS gene polymorphism and promoter methylation‐mediating effects on the efficacy of folate therapy in patients with hyperhomocysteinemia

“…It often occurs in the CpG island located in the promoter region of most genes . The aberrant methylation could lead to abnormal gene expression, subsequently resulting in the occurrence of diseases . Recently, a study revealed that DNA methylation partly mediated the effects of gene polymorphisms on disease occurrence .…”

“…12 The aberrant methylation could lead to abnormal gene expression, subsequently resulting in the occurrence of diseases. 13,14 Recently, a study revealed that DNA methylation partly mediated the effects of gene polymorphisms on disease occurrence. 15 Nevertheless, no studies have analyzed whether the CBS gene polymorphism and promoter methylation affect the efficacy of HHcy with folate therapy.…”

Association of global DNA hypomethylation with post‐operative cognitive dysfunction in elderly patients undergoing hip surgery

“…Many studies revealed that global methylation was one of the earliest molecular changes in the transition from a normal to a diseased cell . Aberrant DNA methylation in peripheral leukocytes of patients with cancer, diabetes, and cardiovascular disease has been reported . In addition, Melas's group reported significant leukocyte DNA hypomethylation in patients with schizophrenia, which could be rescued with antipsychotic medication .…”