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Impacts of the Mitochondrial Genome on the Relationship of Long-Term Ambient Fine Particle Exposure with Blood DNA Methylation Age.

ABSTRACT: The mitochondrial genome has long been implicated in age-related disease, but no studies have examined its role in the relationship of long-term fine particle (PM2.5) exposure and DNA methylation age (DNAm-age)-a novel measure of biological age. In this analysis based on 940 observations between 2000 and 2011 from 552 Normative Aging Study participants, we determined the roles of mitochondrial DNA haplogroup variation and mitochondrial genome abundance in the relationship of PM2.5 with DNAm-age. We used the GEOS-chem transport model to estimate address-specific, one-year PM2.5 levels for each participant. DNAm-age and mitochondrial DNA markers were measured from participant blood samples. Nine haplogroups (H, I, J, K, T, U, V, W, and X) were present in the population. In fully adjusted linear mixed-effects models, the association of PM2.5 with DNAm-age (in years) was significantly diminished in carriers of haplogroup V (Pinteraction = 0.01; ? = 0.18, 95%CI: -0.41, 0.78) compared to noncarriers (? = 1.25, 95%CI: 0.58, 1.93). Mediation analysis estimated that decreases in mitochondrial DNA copy number, a measure of mitochondrial genome abundance, mediated 12% of the association of PM2.5 with DNAm-age. Our data suggests that the mitochondrial genome plays a role in DNAm-age relationships particularly in the context of long-term PM2.5 exposure.

SUBMITTER: Nwanaji-Enwerem JC

PROVIDER: S-EPMC5555236 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Impacts of the Mitochondrial Genome on the Relationship of Long-Term Ambient Fine Particle Exposure with Blood DNA Methylation Age.

Nwanaji-Enwerem Jamaji C JC Colicino Elena E Dai Lingzhen L Cayir Akin A Sanchez-Guerra Marco M Laue Hannah E HE Nguyen Vy T VT Di Qian Q Just Allan C AC Hou Lifang L Vokonas Pantel P Coull Brent A BA Weisskopf Marc G MG Baccarelli Andrea A AA Schwartz Joel D JD

Environmental science & technology 20170707 14

The mitochondrial genome has long been implicated in age-related disease, but no studies have examined its role in the relationship of long-term fine particle (PM<sub>2.5</sub>) exposure and DNA methylation age (DNAm-age)-a novel measure of biological age. In this analysis based on 940 observations between 2000 and 2011 from 552 Normative Aging Study participants, we determined the roles of mitochondrial DNA haplogroup variation and mitochondrial genome abundance in the relationship of PM<sub>2. ...[more]

PMID: 28636816

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Project description:BackgroundSeveral epigenome-wide association studies (EWAS) of ambient particulate matter with aerodynamic diameter ≤ 2.5 µm (PM2.5) have been reported. However, EWAS of PM2.5 elements (PEs), reflecting different emission sources, are very limited.ObjectivesWe performed EWAS of short- and intermediate-term exposure to PM2.5 and 13 PEs. We hypothesized that significant changes in DNAm may vary by PM2.5 mass and its elements.MethodsWe repeatedly collected blood samples in the Normative Aging Study and measured leukocyte DNA methylation (DNAm) with the Illumina HumanMethylation450K BeadChip. We collected daily PM2.5 and 13 PEs at a fixed central site. To estimate the associations between each PE and DNAm at individual cytosine-phosphate-guanine (CpG) sites, we incorporated a distributed-lag (0-27 d) term in the setting of median regression with subject-specific intercept and examined cumulative lag associations. We also accounted for selection bias due to loss to follow-up and mortality prior to enrollment. Significantly differentially methylated probes (DMPs) were identified using Bonferroni correction for multiple testing. We further conducted regional and pathway analyses to identify significantly differentially methylated regions (DMRs) and pathways.ResultsWe included 695 men with 1,266 visits between 1999 and 2013. The subjects had a mean age of 75 years. The significant DMPs, DMRs, and pathways varied by to PM2.5 total mass and PEs. For example, PM2.5 total mass was associated with 2,717 DMPs and 10,470 DMRs whereas Pb was associated with 3,173 DMPs and 637 DMRs. The identified pathways by PM2.5 mass were mostly involved in mood disorders, neuroplasticity, immunity, and inflammation, whereas the pathways associated with motor vehicles (BC, Cu, Pb, and Zn) were related with cardiovascular disease and cancer (e.g., "PPARs signaling").ConclusionsPM2.5 and PE were associated with methylation changes at multiple probes and along multiple pathways, in ways that varied by particle components.

Project description:BackgroundChronic kidney disease (CKD) is a serious global public health challenge, but there is limited information on the connection between air pollution and risk of CKD.ObjectiveThe aim of this study was to investigate the association between long-term exposure to particulate matter (PM) with an aerodynamic diameter of less than [Formula: see text] ([Formula: see text]) and the development of CKD in a large cohort.MethodsA total of 100,629 nonCKD Taiwanese residents age 20 y or above were included in this study between 2001 and 2014. Ambient [Formula: see text] concentration was estimated at each participant's address using a satellite-based spatiotemporal model. Incident CKD cases were identified by an estimated glomerular filtration rate (eGFR) of less than [Formula: see text]. We collected information on a wide range of potential confounders/modifiers during the medical examinations. Cox proportional hazard regression was applied to calculate hazard ratios (HRs).ResultsDuring the follow-up, 4,046 incident CKD cases were identified, and the incidence rate was 6.24 per 1,000 person-years. In contrast with participants with the first quintile exposure of [Formula: see text], participants with the fourth and fifth quintiles exposure of [Formula: see text] had increased risk of CKD development, adjusting for age, sex, educational level, smoking, drinking, body mass index, systolic blood pressure, fasting glucose, total cholesterol, and self-reported heart disease or stroke, with an HR [95% confidence interval (CI)] of 1.11 (1.02, 1.22) and 1.15 (1.05, 1.26), respectively. A significant concentration-response trend was observed ([Formula: see text]). Every [Formula: see text] increment in the [Formula: see text] concentration was associated with a 6% higher risk of developing CKD (HR: 1.06, 95% CI: 1.02, 1.10). Sensitivity and stratified analyses yielded similar results.ConclusionsLong-term exposure to ambient [Formula: see text] was associated with an increased risk of CKD development. Our findings reinforce the urgency to develop global strategies of air pollution reduction to prevent CKD. https://doi.org/10.1289/EHP3304.

Dataset Information

Impacts of the Mitochondrial Genome on the Relationship of Long-Term Ambient Fine Particle Exposure with Blood DNA Methylation Age.

Publications

Impacts of the Mitochondrial Genome on the Relationship of Long-Term Ambient Fine Particle Exposure with Blood DNA Methylation Age.

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