Journal Article

DNA Methylation as a Biomarker for Cardiovascular Disease Risk

Long, Tiffany I., Yu, Mimi C., Arakawa, Kazuko, Wang, Renwei, Laird, Peter W., Kim, Myungjin

2010

Overview

Elevated serum homocysteine is associated with an increased risk of cardiovascular disease (CVD). This may reflect a reduced systemic remethylation capacity, which would be expected to cause decreased genomic DNA methylation in peripheral blood leukocytes (PBL). We examined the association between prevalence of CVD (myocardial infarction, stroke) and its predisposing conditions (hypertension, diabetes) and PBL global genomic DNA methylation as represented by ALU and Satellite 2 (AS) repetitive element DNA methylation in 286 participants of the Singapore Chinese Health Study, a population-based prospective investigation of 63,257 men and women aged 45-74 years recruited during 1993-1998. Men exhibited significantly higher global DNA methylation [geometric mean (95% confidence interval (CI)): 159 (143, 178)] than women [133 (121, 147)] (P = 0.01). Global DNA methylation was significantly elevated in men with a history of CVD or its predisposing conditions at baseline (P = 0.03) but not in women (P = 0.53). Fifty-two subjects (22 men, 30 women) who were negative for these CVD/predisposing conditions at baseline acquired one or more of these conditions by the time of their follow-up I interviews, which took place on average about 5.8 years post-enrollment. Global DNA methylation levels of the 22 incident cases in men were intermediate (AS, 177) relative to the 56 male subjects who remained free of CVD/predisposing conditions at follow-up (lowest AS, 132) and the 51 male subjects with a diagnosis of CVD or predisposing conditions reported at baseline (highest AS 184) (P for trend = 0.0008) No such association was observed in women (P = 0.91). Baseline body mass index was positively associated with AS in both men and women (P = 0.007). Our findings indicate that elevated, not decreased, PBL DNA methylation is positively associated with prevalence of CVD/predisposing conditions and obesity in Singapore Chinese.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Age Factors / Aged / Biochemistry / Biomarkers / Biomarkers - metabolism / Body mass / Body Mass Index / Cardiovascular disease / Cardiovascular diseases / Cardiovascular Diseases - diagnosis / Cardiovascular Diseases - ethnology / Cardiovascular Diseases - genetics / Cardiovascular Disorders / Cerebral infarction / Colorectal cancer / Confidence intervals / Deoxyribonucleic acid / Diabetes / Diabetes mellitus / DNA / DNA Methylation / Ethnicity / Family medical history / Female / Genetic research / Genetics and Genomics/Epigenetics / Health risk assessment / Health risks / Homocysteine / Humans / Hypertension / Leukocytes / Leukocytes - cytology / Male / Medicine / Men / Metabolic syndrome / Methylation / Middle Aged / Molecular biology / Myocardial infarction / Peripheral blood / Population studies / Public Health and Epidemiology/Epidemiology / Public Health and Epidemiology/Screening / Risk / Risk factors / Sex Factors / Singapore / Surgery / Vitamin B