Dataset Information

Short-term ambient particle radioactivity level and renal function in older men: Insight from the Normative Aging Study.

ABSTRACT: BACKGROUND:Whole-body and thoracic ionizing radiation exposure are both associated with the development of renal dysfunction. However, whether low-level environmental radiation from air pollution affects renal function remains unknown. OBJECTIVES:We investigated the association of particle radioactivity (PR) with renal function defined by the estimated glomerular filtration rate (eGFR) and chronic kidney disease (CKD) in the Normative Aging Study. METHODS:This longitudinal analysis included 2491 medical visits from 809 white males enrolled between 1999 and 2013. The eGFR was calculated using the CKD-EPI and MDRD equations, and CKD cases were identified as those with an eGFR <60?mL/min/1.73?m2. Gross ? activity measured by five monitors of the U.S. Environmental Protection Agency's RadNet monitoring network was utilized to represent PR. RESULTS:Ambient PR levels from 1 to 28?days prior to clinical visit demonstrated robust negative associations with both forms of eGFR, but not with the increased odds of CKD. An interquartile range higher 28-day average ambient PR level was significantly associated with 0.83-mL/min/1.73?m2 lower eGFR estimated by the CKD-EPI equation (95% confidence interval: -1.46, -0.20, p-value?=?0.01). Controlling for PM2.5 or black carbon in the model slightly attenuated the PR effects on eGFR. However, in individuals with the highest levels (3rd tertile) of C-reactive protein (CRP) or fibrinogen, we observed robust associations of PR with eGFR and CKD, suggesting that systemic inflammation may modify the PR-eGFR and PR-CKD relationships. CONCLUSIONS:Our study reveals adverse health effects of short-term low-level ambient PR on the renal function, providing evidence to guide further study of the interplay between PR, inflammation, and renal health.

SUBMITTER: Gao X

PROVIDER: S-EPMC6728188 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Short-term ambient particle radioactivity level and renal function in older men: Insight from the Normative Aging Study.

Gao Xu X Koutrakis Petros P Blomberg Annelise J AJ Coull Brent B Vokonas Pantel P Schwartz Joel J Baccarelli Andrea A AA

Environment international 20190720

<h4>Background</h4>Whole-body and thoracic ionizing radiation exposure are both associated with the development of renal dysfunction. However, whether low-level environmental radiation from air pollution affects renal function remains unknown.<h4>Objectives</h4>We investigated the association of particle radioactivity (PR) with renal function defined by the estimated glomerular filtration rate (eGFR) and chronic kidney disease (CKD) in the Normative Aging Study.<h4>Methods</h4>This longitudinal ...[more]

PMID: 31336254

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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:Current studies indicate that long-term exposure to ambient fine particulate matter (PM2.5) is related with global mortality, yet no studies have explored relationships of PM2.5 and its species with DNAm PhenoAge acceleration (DNAmPhenoAccel), a new epigenetic biomarker of phenotypic age. We identified which PM2.5 species had association with DNAmPhenoAccel in a one-year exposure window in a longitudinal cohort. We collected whole blood samples from 683 elderly men in the Normative Aging Study between 1999 and 2013 (n = 1254 visits). DNAm PhenoAge was calculated using 513 CpGs retrieved from the Illumina Infinium HumanMethylation450 BeadChip. Daily concentrations of PM2.5 species were measured at a fixed air-quality monitoring site and one-year moving averages were computed. Linear mixed-effect (LME) regression and Bayesian kernel machine (BKM) regression were used to estimate the associations. The covariates included chronological age, body mass index (BMI), cigarette pack years, smoking status, estimated cell types, batch effects etc. Benjamini-Hochberg false discovery rate at a 5% false positive threshold was used to adjust for multiple comparison. During the study period, the mean DNAm PhenoAge and chronological age in our subjects were 68 and 73 years old, respectively. Using LME model, only lead and calcium were significantly associated with DNAmPhenoAccel. For example, an interquartile range (IQR, 0.0011 ?g/m3) increase in lead was associated with a 1.29-year [95% confidence interval (CI): 0.47, 2.11] increase in DNAmPhenoAccel. Using BKM model, we selected PM2.5, lead, and silicon to be predictors for DNAmPhenoAccel. A subsequent LME model showed that only lead had significant effect on DNAmPhenoAccel: 1.45-year (95% CI: 0.46, 2.46) increase in DNAmPhenoAccel following an IQR increase in one-year lead. This is the first study that investigates long-term effects of PM2.5 components on DNAmPhenoAccel. The results demonstrate that lead and calcium contained in PM2.5 was robustly associated with DNAmPhenoAccel.

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Dataset Information

Short-term ambient particle radioactivity level and renal function in older men: Insight from the Normative Aging Study.

Publications

Short-term ambient particle radioactivity level and renal function in older men: Insight from the Normative Aging Study.

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