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

Matthew R Rytel,E Andres Houseman,Rondi Butler,Joseph M Braun,Karl T Kelsey,Melissa Eliot

doi:10.1186/s12940-021-00717-y

Abstract

BackgroundBetween 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).MethodsWe 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.ResultsEpigenome-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.ConclusionWe 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.

Highlights

Between 1962 and 1971, the US Air Force sprayed Agent Orange across Vietnam, exposing many soldiers to this dioxin-containing herbicide
Since dioxin is known to interact with genes in the aryl hydrocarbon (dioxin) receptor (AHR) pathway, members of this pathway were examined for TCDD serum associated methylation alterations, but no Control (N = 12) Low (N = 3)
We evaluated the DNA methylation of the adipose tissue and whole blood of a pilot-sized subset of Operation Ranch Hand veterans who were exposed to Agent Orange while serving in the Vietnam War

Summary

Introduction

Between 1962 and 1971, the US Air Force sprayed Agent Orange across Vietnam, exposing many soldiers to this dioxin-containing herbicide. 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). After the end of Operation Ranch Hand, the veterans reported health issues that they believed were related to their Agent Orange exposure [4]. This prompted the Air Force to launch a prospective, longitudinal study in 1982 termed the Air Force Health Study (AFHS), which was designed to track morbidity of the Ranch Hand veterans [4]. Targeting our analysis on methylation in the DNA of adipose and whole blood tissue samples collected as part of the AFHS, we sought to characterize the effect of TCDD exposure on the epigenome of the Ranch Hand veterans

Methods

Results

Discussion

Conclusion