Association between global leukocyte DNA methylation and cardiovascular risk in postmenopausal women | BMC Medical Genetics | Full Text

Association between global leukocyte DNA methylation and cardiovascular risk in postmenopausal women | BMC Medical Genetics | Full Text

BMC Medical Genetics

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

• Ramon Bossardi Ramos,
• Vitor Fabris,
• Sheila Bunecker Lecke,
• Maria Augusta Maturana and
• Poli Mara SpritzerEmail author

BMC Medical GeneticsBMC series – open, inclusive and trusted201617:71

DOI: 10.1186/s12881-016-0335-x

©  The Author(s). 2016

Received: 6 December 2015

Accepted: 5 October 2016

Published: 10 October 2016

Open Peer Review reports

Abstract

Background

Genetic 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.

Methods

In 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).

Results

Age, 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).

Conclusions

Our results indicate that lower global DNA methylation is associated with higher cardiovascular risk in postmenopausal women.

Keywords

Epigenetics 5-methylcytosine Aging Post-menopause Cardiovascular diseases