Exposure to Polycyclic Aromatic Hydrocarbons and Accelerated DNA Methylation Aging.
Exposure to Polycyclic Aromatic Hydrocarbons and Accelerated DNA Methylation Aging.
复制标题
接触多环芳烃和加速 DNA 甲基化老化
DOI：
10.1289/ehp2773
复制
发表时间：
2018-06
影响因子：
10.4
通讯作者：
Wu T
中科院分区：
文献类型：
--
作者：
Li J;Zhu X;Yu K;Jiang H;Zhang Y;Wang B;Liu X;Deng S;Hu J;Deng Q;Sun H;Guo H;Zhang X;Chen W;Yuan J;He M;Bai Y;Han X;Liu B;Liu C;Guo Y;Zhang B;Zhang Z;Hu FB;Gao W;Li L;Lathrop M;Laprise C;Liang L;Wu T
背景：衰老与发病率和死亡率的增加有关，并受环境因素的影响。暴露于多环芳烃（PAHs）与不良健康结果相关;但这种暴露与DNA甲基化衰老（一种新的衰老标志物）的关联尚不清楚。目的：我们的目的是调查多环芳烃暴露与甲基化衰老的关系。研究方法：我们使用989名中国人和160名白人的全血甲基化数据训练并验证了适合中国人群的甲基化年龄预测因子。我们定义了两个老化指标：Δ年龄，甲基化年龄减去实际年龄;老化率，甲基化与实际年龄的比值。在3组健康中国受试者（N=539，在上述989名中国受试者中）中使用线性回归评价PAH暴露与衰老指标的相关性，这些受试者的暴露水平通过10种尿单羟基PAH代谢产物进行评估。结果如下：我们开发了一个甲基化年龄预测器，在中国人和高加索人中均提供准确的预测（R=0.94-0.96，RMSE=3.8-4.3）。在我们测量的10种尿代谢物中，1-羟基芘和9-羟基菲与甲基化衰老相关，与其他OH-PAH和危险因素无关; 1-羟基芘增加1个单位与Δ年龄增加0.53年相关[95%置信区间（CI）：0.18，0.88;错误发现率（FDR）FDR=0.004]和老化率增加1.17（95% CI：0.36，1.98; FDR=0.02），而对于9-羟基菲，Δ年龄增加0.54-y（95% CI：0.17，0.91; FDR=0.004），老化率为1.15%（95% CI：0.31，1.99; FDR=0.02）。三个中国样本组的关联方向一致，关联幅度与样本组的暴露水平相关;通过纯化白细胞的甲基化数据验证了关联性。发现几种胞嘧啶-磷酸鸟嘌呤，包括位于FHL 2和FHLVL 2上的胞嘧啶-磷酸鸟嘌呤，与衰老指标和单羟基-PAH水平相关。结论：我们开发了一个甲基化年龄预测器，对中国人群特异，但对高加索人群也准确。我们的研究结果表明，暴露于多环芳烃可能与人类衰老和表观遗传改变的不利影响，在中国人群。https://doi.org/10.1289/EHP2773
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: Δage, 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 Δage [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 Δage (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