Dataset Information

Exposure to Polycyclic Aromatic Hydrocarbons and Accelerated DNA Methylation Aging.

ABSTRACT: BACKGROUND:Aging is related to an increased risk of morbidity and mortality and is affected by environmental factors. Exposure to polycyclic aromatic hydrocarbons (PAHs) is associated with adverse health outcomes; but the association of such exposure with DNA methylation aging, a novel aging marker, is unclear. OBJECTIVES:Our aim was to investigate the association of PAH exposure with methylation aging. METHODS:We trained and validated a methylation age predictor suitable for Chinese populations using whole blood methylation data in 989 Chinese and 160 Caucasians. We defined two aging indicators: ?age, as methylation age minus chronological age; and aging rate, the ratio of methylation to chronological age. The association of PAH exposure with aging indicators was evaluated using linear regressions in three panels of healthy Chinese participants (N=539, among the aforementioned 989 Chinese participants) whose exposure levels were assessed by 10 urinary monohydroxy-PAH metabolites. RESULTS:We developed a methylation age predictor providing accurate predictions in both Chinese individuals and Caucasian persons (R=0.94-0.96, RMSE=3.8-4.3). Among the 10 urinary metabolites that we measured, 1-hydroxypyrene and 9-hydroxyphenanthrene were associated with methylation aging independently of other OH-PAHs and risk factors; 1-unit increase in 1-hydroxypyrene was associated with a 0.53-y increase in ?age [95% confidence interval (CI): 0.18, 0.88; false discovery rate (FDR) FDR=0.004] and 1.17% increase in aging rate (95% CI: 0.36, 1.98; FDR=0.02), whereas for 9-hydroxyphenanthrene, the increase was 0.54-y for ?age (95% CI: 0.17, 0.91; FDR=0.004), and 1.15% for aging rate (95% CI: 0.31, 1.99; FDR=0.02). The association direction was consistent across the three Chinese panels with the association magnitude correlating with the panels' exposure levels; the association was validated by methylation data of purified leukocytes. Several cytosine-phosphoguanines, including those located on FHL2 and ELOVL2, were found associated with both aging indicators and monohydroxy-PAH levels. CONCLUSIONS:We developed a methylation age predictor specific for Chinese populations but also accurate for Caucasian populations. Our findings suggest that exposure to PAHs may be associated with an adverse impact on human aging and epigenetic alterations in Chinese populations. https://doi.org/10.1289/EHP2773.

SUBMITTER: Li J

PROVIDER: S-EPMC6108582 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Exposure to Polycyclic Aromatic Hydrocarbons and Accelerated DNA Methylation Aging.

Li Jun J Zhu Xiaoyan X Yu Kuai K Jiang Haijing H Zhang Yizhi Y Wang Biqi B Liu Xuezhen X Deng Siyun S Hu Jie J Deng Qifei Q Sun Huizhen H Guo Huan H Zhang Xiaomin X Chen Weihong W Yuan Jing J He Meian M Bai Yansen Y Han Xu X Liu Bing B Liu Chuanyao C Guo Yanjun Y Zhang Bing B Zhang Zhihong Z Hu Frank B FB Gao Wenjing W Li Liming L Lathrop Mark M Laprise Catherine C Liang Liming L Wu Tangchun T

Environmental health perspectives 20180614 6

<h4>Background</h4>Aging is related to an increased risk of morbidity and mortality and is affected by environmental factors. Exposure to polycyclic aromatic hydrocarbons (PAHs) is associated with adverse health outcomes; but the association of such exposure with DNA methylation aging, a novel aging marker, is unclear.<h4>Objectives</h4>Our aim was to investigate the association of PAH exposure with methylation aging.<h4>Methods</h4>We trained and validated a methylation age predictor suitable f ...[more]

PMID: 29906262

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Project description:In a longitudinal cohort of approximately 700 children in New York City, the prevalence of asthma (>25%) is among the highest in the US. This high risk may in part be caused by transplacental exposure to traffic-related polycyclic aromatic hydrocarbons (PAHs) but biomarkers informative of PAH-asthma relationships is lacking. We here hypothesized that epigenetic marks associated with transplacental PAH exposure and/or childhood asthma risk could be identified in fetal tissues. Mothers completed personal prenatal air monitoring for PAH exposure determination. Methylation sensitive restriction fingerprinting was used to analyze umbilical cord white blood cell (UCWBC) DNA of 20 cohort children. Over 30 DNA sequences were identified whose methylation status was dependent on the level of maternal PAH exposure. Six sequences were found to be homologous to known genes having one or more 5'-CpG island(s) (5'-CGI). Of these, acyl-CoA synthetase long-chain family member 3 (ACSL3) exhibited the highest concordance between the extent of methylation of its 5'-CGI in UCWBCs and the level of gene expression in matched fetal placental tissues in the initial 20 cohort children. ACSL3 was therefore chosen for further investigation in a larger sample of 56 cohort children. Methylation of the ACSL3 5'-CGI was found to be significantly associated with maternal airborne PAH exposure exceeding 2.41 ng/m(3) (OR = 13.8; p<0.001; sensitivity = 75%; specificity = 82%) and with a parental report of asthma symptoms in children prior to age 5 (OR = 3.9; p<0.05). Thus, if validated, methylated ACSL3 5'CGI in UCWBC DNA may be a surrogate endpoint for transplacental PAH exposure and/or a potential biomarker for environmentally-related asthma. This exploratory report provides a new blueprint for the discovery of epigenetic biomarkers relevant to other exposure assessments and/or investigations of exposure-disease relationships in birth cohorts. The results support the emerging theory of early origins of later life disease development.

Dataset Information

Exposure to Polycyclic Aromatic Hydrocarbons and Accelerated DNA Methylation Aging.

Publications

Exposure to Polycyclic Aromatic Hydrocarbons and Accelerated DNA Methylation Aging.

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