Exposure to polycyclic aromatic hydrocarbons and accelerated DNA methylation ageing: an observational study

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• 作者：Jun Li ; MD^a ; ^b ; ^&dagger ; ; Xiaoyan Zhu ; MD^a ; ^&dagger ; ; Siyun Deng ; MD^a ; Xuezhen Liu ; MD^a ; Qifei Deng ; MD^a ; Kuai Yu ; MD^a ; Huizhen Sun ; MD^a ; Prof Xiaomin Zhang ; PhD^a ; Prof Huan Guo ; PhD^a ; Prof Weihong Chen ; PhD^a ; Prof Jing Yuan ; PhD^a ; Dan Kuang ; MD^a ; Prof Meian He ; PhD^a ; Yansen Bai ; MD^a ; Xu Han ; MD^a ; Bing Liu ; MD^a ; Yizhi Zhang ; MD^a ; Haijing Jiang ; MD^a ; Prof Longxian Cheng ; MD^c ; Xiaoting Luo ; MD^d ; Wenhua Mei ; MD^d ; Zhiming Zhou ; MD^e ; Shunchang Sun ; MD^e ; Xiaosheng He ; MD^a ; Liyun Zhang ; MD^f ; Chuanyao Liu ; MD^a ; Yanjun Guo ; MD^a ; Bing Zhang ; MD^a ; Zhihong Zhang ; MD^a ; Prof Frank B Hu ; MD^b ; ^g ; ^h ; Prof Liming Liang ; PhD^b ; ⁱ ; ^&dagger ; ; ^{lliang@hsph.harvard.edu" class="auth_mail" title="E-mail the corresponding author} ; Prof Tangchun Wu ; MD^a ; ^&dagger ; ; ^{wut@mails.tjmu.edu.cn" class="auth_mail" title="E-mail the corresponding author}
• 刊名：The Lancet
• 出版年：2015
• 出版时间：October 2015
• 年：2015
• 卷：386
• 期：supp_S1
• 页码：S20
• 全文大小：62 K

文摘

Ageing is related to the risk of many diseases and is affected by genetic, epigenetic, and environmental factors. Exposure to the ubiquitous pollutant polycyclic aromatic hydrocarbons (PAHs) is known to cause health damage, but the relation between such exposure with methylation ageing has not been studied. We undertook an association analysis of exposure to PAHs and DNA methylation ageing, a novel and promising ageing marker.

Methods

We built a model of methylation age and defined two ageing indicators (ageing rate, calculated as ratio of methylation to chronological age; and Δage, calculated as methylation minus chronological age) on the basis of genome-wide methylation data of blood in five panels of Chinese individuals (N=596). Participants included 137 coke oven workers (aged 26–60 years) who were chronically and occupationally exposed to high levels of PAHs; 101 patients with acute coronary syndrome (aged 40–86 years) from Wuhan, China; 97 patients with this syndrome (aged 38–83 years) from Guangdong, China; 162 healthy individuals (aged 26–79 years) from Wuhan; and 99 healthy individuals (aged 37–80 years) from Zhuhai, China. Exposure to individual PAHs was assessed by ten urinary PAH metabolites. We examined the relations between PAH exposure and the two ageing indicators, and investigated the potential CpGs mediating the association. Written informed consent was obtained from all participants. Our study was approved by the ethics committee of Tongji Medical College, Wuhan, China. No study subjects were from clinical trials.

Findings

Coke oven workers, who were exposed to high levels of PAHs at work (mean nature-log-transformed total urinary PAHs −1·909 [SD 0·461]), had significant age acceleration (2·7% increase in ageing rate [p=0·002] and 1·218-year increase in Δage [p=0·01] compared with all other panels). Urinary 3-OH-phenanthrene and 9-OH-phenanthrene were independently and significantly associated with the two ageing indicators in our non-disease panels. One unit increase of nature-log-transformed 9-OH-phenanthrene was associated with a 1·8% increase (p=0·0029) in ageing rate and a 1·1-year increase (p=0·0002) in Δage, whereas for 3-OH-phenanthrene the increase was 1·3% (p=0·0050) for ageing rate and 0·57 year (p=0·0109) for Δage. Methylation at several ageing-related and PAH-related CpGs (annotated on ELOVL2, KLHL35, FHL2, BOK, PDP1, and OTUD7A) was reported to mediate the effect of PAH exposure on methylation ageing.

Interpretation

Our study revealed a significant association between PAH exposure and accelerated methylation ageing. The importance of exposure-related ageing needs to be further investigated.

Funding

National Key Basic Research and Development Program, Natural National Scientific Foundation, the 111 Project, the Program for Changjiang Scholars, and Innovative Research Team Scholars.