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Air pollution and DNA methylation: interaction by psychological factors in the VA Normative Aging Study.

ABSTRACT: DNA methylation is a potential pathway linking air pollution to disease. Studies indicate that psychological functioning modifies the association between pollution and morbidity. The authors estimated the association of DNA methylation with ambient particulate matter less than 2.5 µm in diameter (PM(2.5)) and black carbon, using mixed models. DNA methylation of the inducible nitric oxide synthase gene, iNOS, and the glucocorticoid receptor gene, GCR, was measured by quantitative polymerase chain reaction pyrosequencing of 1,377 blood samples from 699 elderly male participants in the VA Normative Aging Study (1999-2009). The authors also investigated whether this association was modified by psychological factors including optimism or pessimism, anxiety, and depression. iNOS methylation was decreased after acute exposure to both black carbon and PM(2.5). A 1-μg/m(3) increase in exposure to black carbon in the 4 hours preceding the clinical examination was associated with a 0.9% decrease in 5-methylcytosine (95% CI: 0.4, 1.4) in iNOS, and a 10-μg/m(3) increase in exposure to PM(2.5) was associated with a 0.6% decrease in 5-methylcytosine (95% CI: 0.03, 1.1) in iNOS. Participants with low optimism and high anxiety had associations that were 3-4 times larger than those with high optimism or low anxiety. GCR methylation was not associated with particulate air pollution exposure.

SUBMITTER: Madrigano J

PROVIDER: S-EPMC3491965 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

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Air pollution and DNA methylation: interaction by psychological factors in the VA Normative Aging Study.

Madrigano Jaime J Baccarelli Andrea A Mittleman Murray A MA Sparrow David D Spiro Avron A Vokonas Pantel S PS Cantone Laura L Kubzansky Laura L Schwartz Joel J

American journal of epidemiology 20120712 3

DNA methylation is a potential pathway linking air pollution to disease. Studies indicate that psychological functioning modifies the association between pollution and morbidity. The authors estimated the association of DNA methylation with ambient particulate matter less than 2.5 µm in diameter (PM(2.5)) and black carbon, using mixed models. DNA methylation of the inducible nitric oxide synthase gene, iNOS, and the glucocorticoid receptor gene, GCR, was measured by quantitative polymerase chain ...[more]

PMID: 22798479

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Project description:Epidemiological studies have reported associations between particulate matter (PM) concentrations and cancer and respiratory and cardiovascular diseases. DNA methylation has been identified as a possible link but so far it has only been analyzed in candidate sites.We studied the association between DNA methylation and short- and mid-term air pollution exposure using genome-wide data and identified potential biological pathways for additional investigation.We collected whole blood samples from three independent studies-KORA F3 (2004-2005) and F4 (2006-2008) in Germany, and the Normative Aging Study (1999-2007) in the United States-and measured genome-wide DNA methylation proportions with the Illumina 450k BeadChip. PM concentration was measured daily at fixed monitoring stations and three different trailing averages were considered and regressed against DNA methylation: 2-day, 7-day and 28-day. Meta-analysis was performed to pool the study-specific results.Random-effect meta-analysis revealed 12 CpG (cytosine-guanine dinucleotide) sites as associated with PM concentration (1 for 2-day average, 1 for 7-day, and 10 for 28-day) at a genome-wide Bonferroni significance level (p ? 7.5E-8); 9 out of these 12 sites expressed increased methylation. Through estimation of I2 for homogeneity assessment across the studies, 4 of these sites (annotated in NSMAF, C1orf212, MSGN1, NXN) showed p > 0.05 and I2 < 0.5: the site from the 7-day average results and 3 for the 28-day average. Applying false discovery rate, p-value < 0.05 was observed in 8 and 1,819 additional CpGs at 7- and 28-day average PM2.5 exposure respectively.The PM-related CpG sites found in our study suggest novel plausible systemic pathways linking ambient PM exposure to adverse health effect through variations in DNA methylation.Panni T, Mehta AJ, Schwartz JD, Baccarelli AA, Just AC, Wolf K, Wahl S, Cyrys J, Kunze S, Strauch K, Waldenberger M, Peters A. 2016. A genome-wide analysis of DNA methylation and fine particulate matter air pollution in three study populations: KORA F3, KORA F4, and the Normative Aging Study. Environ Health Perspect 124:983-990;?http://dx.doi.org/10.1289/ehp.1509966.

Project description:BackgroundAir pollution has been related to mean changes in outcomes, including DNA methylation. However, mean regression analyses may not capture associations that occur primarily in the tails of the outcome distribution.ObjectivesIn this study, we examined whether the association between particulate air pollution and DNA methylation differs across quantiles of the methylation distribution. We focused on methylation of candidate genes related to coagulation and inflammation: coagulation factor III (F3), intercellular adhesion molecule 1 (ICAM-1), interferon gamma (IFN-?), interleukin-6 (IL-6), and toll-like receptor 2 (TRL-2).MethodsWe measured gene-specific blood DNA methylation repeatedly in 777 elderly men participating in the Normative Aging Study (1999-2010). We fit quantile regressions for longitudinal data to investigate whether the associations of particle number, PM2.5 (diameter ? 2.5 ?m)black carbon, and PM2.5 mass concentrations (4-week moving average) with DNA methylation [expressed as the percentage of methylated cytosines over the sum of methylated and unmethylated cytosines at position 5 (%5mC)] varied across deciles of the methylation distribution. We reported the quantile regression coefficients that corresponded to absolute differences in DNA methylation (expressed in %5mC) associated with an interquartile range increase in air pollution concentration.ResultsInterquartile range increases in particle number, PM2.5 black carbon, and PM2.5 mass concentrations were associated with significantly lower methylation in the lower tails of the IFN-? and ICAM-1 methylation distributions. For instance, a 3.4-?g/m3 increase in PM2.5 mass concentration was associated with a 0.18%5mC (95% CI: -0.30, -0.06) decrease on the 20th percentile of ICAM-1 methylation, but was not significantly related to the 80th percentile (estimate: 0.07%5mC, 95% CI: -0.09, 0.24).ConclusionsIn our study population of older men, air pollution exposures were associated with a left shift in the lower tails of the IFN-? and ICAM-1 methylation distributions.

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Dataset Information

Air pollution and DNA methylation: interaction by psychological factors in the VA Normative Aging Study.

Publications

Air pollution and DNA methylation: interaction by psychological factors in the VA Normative Aging Study.

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