Tellez-Plaza Maria, Tang Wan-Yee, Shang Yan, Umans Jason G, Francesconi Kevin A, Goessler Walter, Ledesma Marta, Leon Montserrat, Laclaustra Martin, Pollak Jonathan, Guallar Eliseo, Cole Shelley A, Fallin M Dani, Navas-Acien Ana
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
Environ Health Perspect. 2014 Sep;122(9):946-54. doi: 10.1289/ehp.1306674. Epub 2014 Apr 25.
The association between human blood DNA global methylation and global hydroxymethylation has not been evaluated in population-based studies. No studies have evaluated environmental determinants of global DNA hydroxymethylation, including exposure to metals.
We evaluated the association between global DNA methylation and global DNA hydroxymethylation in 48 Strong Heart Study participants for which selected metals had been measured in urine at baseline and DNA was available from 1989-1991 (visit 1) and 1998-1999 (visit 3).
We measured the percentage of 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) in samples using capture and detection antibodies followed by colorimetric quantification. We explored the association of participant characteristics (i.e., age, adiposity, smoking, and metal exposure) with both global DNA methylation and global DNA hydroxymethylation.
The Spearman's correlation coefficient for 5-mC and 5-hmC levels was 0.32 (p = 0.03) at visit 1 and 0.54 (p < 0.001) at visit 3. Trends for both epigenetic modifications were consistent across potential determinants. In cross-sectional analyses, the odds ratios of methylated and hydroxymethylated DNA were 1.56 (95% CI: 0.95, 2.57) and 1.76 (95% CI: 1.07, 2.88), respectively, for the comparison of participants above and below the median percentage of dimethylarsinate. The corresponding odds ratios were 1.64 (95% CI: 1.02, 2.65) and 1.16 (95% CI: 0.70, 1.94), respectively, for the comparison of participants above and below the median cadmium level. Arsenic exposure and metabolism were consistently associated with both epigenetic markers in cross-sectional and prospective analyses. The positive correlation of 5-mC and 5-hmC levels was confirmed in an independent study population.
Our findings support that both epigenetic measures are related at the population level. The consistent trends in the associations between these two epigenetic modifications and the characteristics evaluated, especially arsenic exposure and metabolism, suggest the need for understanding which of the two measures is a better biomarker for environmental epigenetic effects in future large-scale epidemiologic studies.
在基于人群的研究中，尚未评估人类血液DNA整体甲基化与整体羟甲基化之间的关联。也没有研究评估整体DNA羟甲基化的环境决定因素，包括金属暴露情况。
我们在48名参加强心研究的参与者中评估了整体DNA甲基化与整体DNA羟甲基化之间的关联，这些参与者在基线时测量了尿液中的特定金属含量，并且有1989 - 1991年（访视1）和1998 - 1999年（访视3）的DNA样本。
我们使用捕获和检测抗体对样本中的5 - 甲基胞嘧啶（5 - mC）和5 - 羟甲基胞嘧啶（5 - hmC）百分比进行测量，随后进行比色定量分析。我们探究了参与者特征（即年龄、肥胖、吸烟和金属暴露）与整体DNA甲基化和整体DNA羟甲基化之间的关联。
在访视1时，5 - mC和5 - hmC水平的斯皮尔曼相关系数为0.32（p = 0.03），在访视3时为0.54（p < 0.001）。两种表观遗传修饰的趋势在潜在决定因素中是一致的。在横断面分析中，对于二甲基胂酸盐百分比中位数以上和以下的参与者进行比较，甲基化DNA和羟甲基化DNA的优势比分别为1.56（95% CI：0.95，2.57）和1.76（95% CI：1.07，2.88）。对于镉水平中位数以上和以下的参与者进行比较，相应的优势比分别为1.64（95% CI：1.02，2.65）和1.16（95% CI：0.70，1.94）。在横断面和前瞻性分析中，砷暴露和代谢与这两种表观遗传标记均持续相关。在一个独立的研究人群中证实了5 - mC和5 - hmC水平的正相关。
我们的研究结果支持这两种表观遗传测量在人群水平上是相关的。这两种表观遗传修饰与所评估特征之间关联的一致趋势，特别是砷暴露和代谢，表明在未来大规模流行病学研究中需要了解这两种测量方法中哪一种是环境表观遗传效应的更好生物标志物。
