Association of global DNA methylation and global DNA hydroxymethylation with metals and other exposures in human blood DNA samples.
Association of global DNA methylation and global DNA hydroxymethylation with metals and other exposures in human blood DNA samples.
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DOI：
10.1289/ehp.1306674
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发表时间：
2014-09
影响因子：
10.4
通讯作者：
Navas-Acien A
中科院分区：
文献类型：
--
作者：
Tellez-Plaza M;Tang WY;Shang Y;Umans JG;Francesconi KA;Goessler W;Ledesma M;Leon M;Laclaustra M;Pollak J;Guallar E;Cole SA;Fallin MD;Navas-Acien A
背景：人类血液 DNA 整体甲基化和整体羟甲基化之间的关联尚未在基于人群的研究中进行评估。尚无研究评估全球 DNA 羟甲基化的环境决定因素，包括接触金属。目的：我们评估了 48 名强心脏研究参与者的整体 DNA 甲基化和整体 DNA 羟甲基化之间的关联，这些参与者在基线时在尿液中测量了选定的金属，并且 1989-1991 年（访问 1）和 1998-1999 年（访问 3）可获得 DNA。方法：我们使用捕获和检测抗体测量样品中 5-甲基胞嘧啶 (5-mC) 和 5-羟甲基胞嘧啶 (5-hmC) 的百分比，然后进行比色定量。我们探讨了参与者特征（即年龄、肥胖、吸烟和金属暴露）与整体 DNA 甲基化和整体 DNA 羟甲基化的关联。结果：第 1 次访视时 5-mC 和 5-hmC 水平的 Spearman 相关系数为 0.32 (p = 0.03)，第 3 次访视时为 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，对于高于和低于胂酸二甲酯中位百分比的参与者进行比较，甲基化和羟甲基化 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)。对于高于和低于中位镉水平的参与者进行比较，相应的比值比分别为 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，砷暴露和代谢始终与表观遗传标记相关。 5-mC 和 5-hmC 水平的正相关性在一项独立研究人群中得到证实。结论：我们的研究结果支持这两种表观遗传指标在人群水平上是相关的。这两种表观遗传修饰与评估的特征（尤其是砷暴露和代谢）之间关联的一致趋势表明，在未来的大规模流行病学研究中，需要了解这两种措施中的哪一种是环境表观遗传效应的更好的生物标志物。引用: Tellez-Plaza M, Tang WY, Shang Y, Umans JG, Francesconi KA, Goessler W, Ledesma M, Leon M, Laclaustra M, Pollak J, Guallar E, Cole SA, Fallin MD, Navas-Acien A. 2014. 全球 DNA 甲基化和全球 DNA 羟甲基化与人类血液 DNA 样本中金属和其他暴露的关联。环境健康视角 122：946–954； http://dx.doi.org/10.1289/ehp.1306674
Background: 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. Objective: 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). Methods: 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. Results: 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. Conclusions: 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. Citation: Tellez-Plaza M, Tang WY, Shang Y, Umans JG, Francesconi KA, Goessler W, Ledesma M, Leon M, Laclaustra M, Pollak J, Guallar E, Cole SA, Fallin MD, Navas-Acien A. 2014. Association of global DNA methylation and global DNA hydroxymethylation with metals and other exposures in human blood DNA samples. Environ Health Perspect 122:946–954; http://dx.doi.org/10.1289/ehp.1306674
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影响因子：
3.7
作者：
Castillo P;Ibáñez F;Guajardo A;Llanos MN;Ronco AM
通讯作者：
Ronco AM
影响因子：
10.4
作者：
Benbrahim-Tallaa L;Waterland RA;Dill AL;Webber MM;Waalkes MP
通讯作者：
Waalkes MP
影响因子：
3.5
作者：
Bornhorst, JA;Hunt, JW;McMillin, GA
通讯作者：
McMillin, GA
影响因子：
6.1
作者：
Gribble, Matthew O.;Tang, Wan-yee;Shang, Yan;Pollak, Jonathan;Umans, Jason G.;Francesconi, Kevin A.;Goessler, Walter;Silbergeld, Ellen K.;Guallar, Eliseo;Cole, Shelley A.;Fallin, M. Daniele;Navas-Acien, Ana
通讯作者：
Navas-Acien, Ana
DOI：
10.1007/s00428-009-0847-2
发表时间：
2010-01
期刊：
Virchows Archiv : an international journal of pathology
影响因子：
--
作者：
Feinberg AP
通讯作者：
Feinberg AP