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Ischemic heart disease and stroke in relation to blood DNA methylation.

ABSTRACT: Epigenetic features such as DNA hypomethylation have been associated with conditions related to cardiovascular risk. We evaluated whether lower blood DNA methylation in heavily methylated repetitive sequences predicts the risk of ischemic heart disease and stroke.We quantified blood DNA methylation of Long Interspersed Nucleotide Element-1 (LINE-1) repetitive elements through PCR-pyrosequencing in 712 elderly individuals from the Boston-area Normative Aging Study. We estimated risk-factor adjusted relative risks (RRs) for ischemic heart disease and stroke at baseline (242 prevalent cases), and during follow-up (44 new cases; median follow-up, 63 months), as well as subsequent mortality from ischemic heart disease (86 deaths; median follow-up, 75 months).Blood LINE-1 hypomethylation was associated with baseline ischemic heart disease (RR = 2.1 [95% confidence interval = 1.2-4.0] for lowest vs. highest methylation quartile) and for stroke (2.5 [0.9-7.5]). Among participants free of baseline disease, individuals with methylation below the median also had higher risk of developing ischemic heart disease (4.0 [1.8-8.9]) or stroke (5.7 [0.8-39.5]). In the entire cohort, persons with methylation below the median had higher mortality from ischemic heart disease (3.3 [1.3-8.4]) and stroke (2.8 [0.6-14.3]). Total mortality was also increased (2.0 [1.2-3.3]). These results were confirmed in additional regression models using LINE-1 methylation as a continuous variable.Subjects with prevalent IHD and stroke exhibited lower LINE-1 methylation. In longitudinal analyses, persons with lower LINE-1 methylation were at higher risk for incident ischemic heart disease and stroke, and for total mortality.

SUBMITTER: Baccarelli A

PROVIDER: S-EPMC3690659 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature

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Ischemic heart disease and stroke in relation to blood DNA methylation.

Baccarelli Andrea A Wright Robert R Bollati Valentina V Litonjua Augusto A Zanobetti Antonella A Tarantini Letizia L Sparrow David D Vokonas Pantel P Schwartz Joel J

Epidemiology (Cambridge, Mass.) 20101101 6

<h4>Background</h4>Epigenetic features such as DNA hypomethylation have been associated with conditions related to cardiovascular risk. We evaluated whether lower blood DNA methylation in heavily methylated repetitive sequences predicts the risk of ischemic heart disease and stroke.<h4>Methods</h4>We quantified blood DNA methylation of Long Interspersed Nucleotide Element-1 (LINE-1) repetitive elements through PCR-pyrosequencing in 712 elderly individuals from the Boston-area Normative Aging Stu ...[more]

PMID: 20805753

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Project description:BACKGROUND:Long-term exposure to particulate matter (PM) in ambient air has been associated with cardiovascular mortality, but few studies have considered incident disease in relation to PM from different sources. OBJECTIVES:We aimed to study associations between long-term exposure to different types of PM and sources, and incident ischemic heart disease (IHD) and stroke in three Swedish cities. METHODS:Based on detailed emission databases, monitoring data, and high-resolution dispersion models, we calculated source contributions to PM with aerodynamic diameter ?10?m (PM10), PM with aerodynamic diameter ?2.5?m (PM2.5), and black carbon (BC) from road wear, traffic exhaust, residential heating, and other sources in Gothenburg, Stockholm, and Umeå. Registry data for participants from four cohorts were used to obtain incidence of IHD and stroke for first hospitalization or death. We constructed time windows of exposure for same-year, 1- to 5-y, and 6- to 10-y averages preceding incidence from annual averages at residential addresses. Risk estimates were based on random effects meta-analyses of cohort-specific Cox proportional hazard models. RESULTS:We observed 5,166 and 3,119 incident IHD and stroke cases, respectively, in 114,758 participants. Overall, few consistent associations were observed between the different air pollution measures and IHD or stroke incidence. However, same-year levels of ambient locally emitted BC (range: 0.01-4.6??g/m3) were associated with a 4.0% higher risk of incident stroke per interquartile range (IQR), 0.30??g/m3 [95% confidence interval (CI): 0.04, 7.8]. This association was primarily related to BC from traffic exhaust. PM10 (range: 4.4-52??g/m3) and PM2.5 (range: 2.9-22??g/m3) were not associated with stroke. Associations with incident IHD were observed only for PM2.5 exposure from residential heating. DISCUSSION:Few consistent associations were observed between different particulate components and IHD or stroke. However, long-term residential exposure to locally emitted BC from traffic exhaust was associated with stroke incidence. The comparatively low exposure levels may have contributed to the paucity of associations. https://doi.org/10.1289/EHP4757.

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Ischemic heart disease and stroke in relation to blood DNA methylation.

Publications

Ischemic heart disease and stroke in relation to blood DNA methylation.

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