title: Association between global leukocyte DNA methylation and cardiovascular risk in postmenopausal women.
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.
authors.affiliation: Gynecological Endocrinology Unit, Division of Endocrinology, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos, 2350, Porto Alegre, RS, 90035-003, Brazil.
authors.forename: Ramon Bossardi
authors.initials: RB
authors.lastname: Ramos
authors.affiliation: Gynecological Endocrinology Unit, Division of Endocrinology, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos, 2350, Porto Alegre, RS, 90035-003, Brazil.
authors.forename: Vitor
authors.initials: V
authors.lastname: Fabris
authors.affiliation: Gynecological Endocrinology Unit, Division of Endocrinology, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos, 2350, Porto Alegre, RS, 90035-003, Brazil.|Department of Diagnostic Methods, Universidade Federal de Ciências da Saúde de Porto Alegre, Rua Sarmento Leite, 245, Porto Alegre, RS, 90050-170, Brazil.
authors.forename: Sheila Bunecker
authors.initials: SB
authors.lastname: Lecke
authors.affiliation: Gynecological Endocrinology Unit, Division of Endocrinology, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos, 2350, Porto Alegre, RS, 90035-003, Brazil.|Present addresses: Institute of Cardiology of Rio Grande do Sul, Cardiology University Foundation, Avenida Princesa Isabel, 395, Porto Alegre, RS, 90040-371, Brazil.|Unisinos University, Av. Unisinos, 950, São Leopoldo, RS, 93022-000, Brazil.
authors.forename: Maria Augusta
authors.initials: MA
authors.lastname: Maturana
authors.affiliation: Gynecological Endocrinology Unit, Division of Endocrinology, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos, 2350, Porto Alegre, RS, 90035-003, Brazil. spritzer@ufrgs.br.|Laboratory of Molecular Endocrinology, Department of Physiology, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2350, Porto Alegre, RS, 90035-003, Brazil. spritzer@ufrgs.br.
authors.forename: Poli Mara
authors.initials: PM
authors.lastname: Spritzer
mesh_terms: D002318:Cardiovascular Diseases / Q000235:genetics*; D003430:Cross-Sectional Studies; D004247:DNA / Q000097:blood*; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007962:Leukocytes; D008875:Middle Aged; D017698:Postmenopause / Q000235:genetics*; D012307:Risk Factors
chemical_list: D004247:DNA
keywords: 5-methylcytosine; Aging; Cardiovascular diseases; Epigenetics; Post-menopause