非吸烟者体内多环芳烃暴露、DNA 甲基化与心率变异性
Exposure to polycyclic aromatic hydrocarbons, DNA methylation and heart rate variability among non-current smokers.
机构信息
Department of Occupational and Environmental Health, Key Laboratory of Environment and Health, Ministry of Education and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Department of Occupational and Environmental Health, Key Laboratory of Environment and Health, Ministry of Education and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China; Suzhou Center for Disease Prevention and Control, Suzhou, 215004, China.
出版信息
Environ Pollut. 2021 Nov 1;288:117777. doi: 10.1016/j.envpol.2021.117777. Epub 2021 Jul 10.
Polycyclic aromatic hydrocarbons (PAHs) exposure is associated with heart rate variability (HRV) reduction, a widely used marker of cardiovascular autonomic dysfunction. The role of DNA methylation in the relationship between PAHs exposure and decreased HRV is largely unknown. This study aims to explore epigenome-wide DNA methylation changes associated with PAHs exposure and further evaluate their associations with HRV alternations among non-current smokers. We measured 10 mono-hydroxylated PAHs (OH-PAHs) in urine and DNA methylation levels in blood leukocytes among participants from three panels of Chinese non-current smokers (152 in WHZH, 99 in SY, and 53 in COW). We conducted linear regression analyses between DNA methylation and OH-PAHs metabolites with adjustment for age, gender, body mass index, drinking, blood cell counts, and surrogate variables in each panel separately, and combined the results by using inverse-variance weighted fixed-effect meta-analysis to obtain estimates of effect size. The median value of total OH-PAHs ranged from 0.92 × 10 in SY panel (62.6% men) to 13.82 × 10 μmol/mmol creatinine in COW panel (43.4% men). The results showed that methylation levels of cg18223625 (COL20A1) and cg07805771 (SLC16A1) were significantly or marginally significantly associated with urinary 2-hydroxynaphthalene [β(SE) = 0.431(0.074) and 0.354(0.068), FDR = 0.016 and 0.056, respectively], while methylation level of cg09235308 (PLEC1) was positively associated with urinary total OH-PAHs [β(SE) = 0.478(0.079), FDR = 0.004]. Hypermethylations of cg18223625, cg07805771, and cg09235308 were inversely associated with HRV indices among the WHZH and COW non-current smokers. However, we did not observe significant epigenome-wide associations for the other 9 urinary OH-PAHs. These findings provide new evidence that PAHs exposure is linked to differential DNA methylation, which may help better understand the influences of PAHs exposure on HRV alternations.
多环芳烃（PAHs）暴露与心率变异性（HRV）降低有关，HRV 是心血管自主功能障碍的广泛应用标志物。PAHs 暴露与 HRV 降低之间的 DNA 甲基化作用在很大程度上尚不清楚。本研究旨在探讨与 PAHs 暴露相关的全基因组 DNA 甲基化变化，并进一步评估其与非吸烟人群 HRV 改变的相关性。我们测量了三个中国非吸烟人群队列（WHZH 队列 152 例、SY 队列 99 例和 COW 队列 53 例）中尿液中的 10 种单羟基多环芳烃（OH-PAHs）代谢物和血液白细胞中的 DNA 甲基化水平。我们分别在每个队列中通过年龄、性别、体重指数、饮酒、血细胞计数和替代变量对 DNA 甲基化和 OH-PAHs 代谢物进行线性回归分析，然后通过逆方差加权固定效应荟萃分析合并结果，以获得效应大小的估计值。在 SY 队列（62.6%为男性）中，总 OH-PAHs 的中位数范围为 0.92×10-913.82×10-9μmol/mmol 肌酐，在 COW 队列（43.4%为男性）中，总 OH-PAHs 的中位数范围为 0.92×10-913.82×10-9μmol/mmol 肌酐。结果表明，cg18223625（COL20A1）和 cg07805771（SLC16A1）的甲基化水平与尿 2-羟基萘酚[β（SE）=0.431（0.074）和 0.354（0.068）， FDR=0.016 和 0.056]呈显著或边缘显著相关，而 cg09235308（PLEC1）的甲基化水平与尿总 OH-PAHs 呈正相关[β（SE）=0.478（0.079），FDR=0.004]。WHZH 和 COW 非吸烟人群中，cg18223625、cg07805771 和 cg09235308 的超甲基化与 HRV 指标呈负相关。然而，我们没有观察到其他 9 种尿 OH-PAHs 的全基因组表观遗传关联。这些发现为 PAHs 暴露与差异 DNA 甲基化有关提供了新的证据，这可能有助于更好地理解 PAHs 暴露对 HRV 改变的影响。
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