橙剂暴露的“牧场手行动”老兵脂肪组织和全血中的 DNA 甲基化：一项初步研究。

DNA methylation in the adipose tissue and whole blood of Agent Orange-exposed Operation Ranch Hand veterans: a pilot study.

机构信息

Department of Epidemiology, Brown University School of Public Health, Providence, RI, 02912, USA.

Department of Pathology and Laboratory Medicine, Brown University School of Public Health, Providence, RI, 02912, USA.

出版信息

Environ Health. 2021 Apr 13;20(1):43. doi: 10.1186/s12940-021-00717-y.

DOI:10.1186/s12940-021-00717-y

PMID:33849548

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8045317/

Abstract

BACKGROUND

Between 1962 and 1971, the US Air Force sprayed Agent Orange across Vietnam, exposing many soldiers to this dioxin-containing herbicide. Several negative health outcomes have been linked to Agent Orange exposure, but data is lacking on the effects this chemical has on the genome. Therefore, we sought to characterize the impact of Agent Orange exposure on DNA methylation in the whole blood and adipose tissue of veterans enrolled in the Air Force Health Study (AFHS).

METHODS

We received adipose tissue (n = 37) and whole blood (n = 42) from veterans in the AFHS. Study participants were grouped as having low, moderate, or high TCDD body burden based on their previously measured serum levels of dioxin. DNA methylation was assessed using the Illumina 450 K platform.

RESULTS

Epigenome-wide analysis indicated that there were no FDR-significantly methylated CpGs in either tissue with TCDD burden. However, 3 CpGs in the adipose tissue (contained within SLC9A3, LYNX1, and TNRC18) were marginally significantly (q < 0.1) hypomethylated, and 1 CpG in whole blood (contained within PTPRN2) was marginally significantly (q < 0.1) hypermethylated with high TCDD burden. Analysis for differentially methylated DNA regions yielded SLC9A3, among other regions in adipose tissue, to be significantly differentially methylated with higher TCDD burden. Comparing whole blood data to a study of dioxin exposed adults from Alabama identified a CpG within the gene SMO that was hypomethylated with dioxin exposure in both studies.

CONCLUSION

We found limited evidence of dioxin associated DNA methylation in adipose tissue and whole blood in this pilot study of Vietnam War veterans. Nevertheless, loci in the genes of SLC9A3 in adipose tissue, and PTPRN2 and SMO in whole blood, should be included in future exposure analyses.

摘要

背景

1962 年至 1971 年间，美国空军在越南喷洒了橙剂，使许多士兵接触到这种含有二恶英的除草剂。一些负面的健康结果与接触橙剂有关，但缺乏关于这种化学物质对基因组影响的数据。因此，我们试图描述橙剂暴露对参加空军健康研究（AFHS）的退伍军人全血和脂肪组织中 DNA 甲基化的影响。

方法

我们从 AFHS 中的退伍军人那里收到了脂肪组织（n=37）和全血（n=42）。根据他们以前测量的血清二恶英水平，研究参与者被分为低、中、高 TCDD 体负荷组。使用 Illumina 450K 平台评估 DNA 甲基化。

结果

全基因组分析表明，在任何组织中，与 TCDD 负担相关的 FDR 显著甲基化 CpG 都没有。然而，脂肪组织中有 3 个 CpG（位于 SLC9A3、LYNX1 和 TNRC18 内）呈边际显著（q<0.1）低甲基化，全血中有 1 个 CpG（位于 PTPRN2 内）呈边际显著（q<0.1）高甲基化，TCDD 负担较高。差异甲基化 DNA 区域的分析显示，脂肪组织中的 SLC9A3 等区域的差异甲基化与较高的 TCDD 负担显著相关。将全血数据与阿拉巴马州暴露于二恶英的成年人研究进行比较，发现两个研究中基因 SMO 内的一个 CpG 与二恶英暴露呈低甲基化。