scholarly journals Serum dioxin and DNA methylation in the sperm of operation ranch hand veterans exposed to Agent Orange

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Karl T. Kelsey ◽  
Matthew Rytel ◽  
Edward Dere ◽  
Rondi Butler ◽  
Melissa Eliot ◽  
...  

Abstract Background Exposure to the herbicide Agent Orange during the Vietnam War was widespread and is associated with numerous adverse health outcomes. A continuing concern of veterans is the possibility that exposure to the dioxin-containing herbicide might induce adverse reproductive outcomes. We sought to assess whether exposure to Agent Orange in Vietnam was associated with changes in DNA methylation in sperm in a subset of Vietnam veterans who participated in the Air Force Health Study (AFHS). Methods We studied 37 members of the AFHS chosen to have no, low, medium or high exposure to Agent Orange, based upon serum dioxin levels obtained during a series of examinations. DNA from stored semen was extracted and DNA methylation assessed on the Illumina 450 K platform. Results Initial epigenome-wide analysis returned no loci that survived control for false discovery. However, the TEAD3 gene had four different CpG sites that showed loss of DNA methylation associated with dioxin exposure. Analysis assessing regional DNA methylation changes revealed 36 gene regions, including the region of the imprinted gene H19 to have altered DNA methylation associated with high exposure compared to the low exposure group. Additional comparison of our data with sperm DNA methylation data from Russian boys exposed to dioxin found an additional 5 loci that were altered in both studies and exhibited a consistent direction of association. Conclusions Studying a small number of sperm samples from veterans enrolled in the AFHS, we did not find evidence of significant epigenome-wide alterations associated with exposure to Agent Orange. However, additional analysis showed that the H19 gene region is altered in the sperm of Agent Orange-exposed Ranch Hand veterans. Our study also replicated several findings of a prior study of dioxin-exposed Russian boys. These results provide additional candidate loci for further investigation and may have implications for the reproductive health of dioxin-exposed individuals.

2020 ◽  
Author(s):  
Matthew Rae Rytel ◽  
Rondi Butler ◽  
Melissa Eliot ◽  
Joseph M. Braun ◽  
E. Andres Houseman ◽  
...  

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 450K 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.


2020 ◽  
Vol 96 ◽  
pp. 27-35
Author(s):  
Jamaji C. Nwanaji-Enwerem ◽  
Timothy G. Jenkins ◽  
Elena Colicino ◽  
Andres Cardenas ◽  
Andrea A. Baccarelli ◽  
...  

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Matthew R. Rytel ◽  
Rondi Butler ◽  
Melissa Eliot ◽  
Joseph M. Braun ◽  
E. Andres Houseman ◽  
...  

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.


1996 ◽  
Vol 30 (5) ◽  
pp. 600-613 ◽  
Author(s):  
David A. Grayson ◽  
Richard P. Marshall ◽  
Matthew Dobson ◽  
Brian I. O'toole ◽  
Ralph J. Schureck ◽  
...  

Objective: The objective of the present paper is to present comprehensive models of the current psychosocial morbidity of Australian Vietnam veterans. Seldom has research in this area attempted to ‘untangle’ direct and indirect influences on current functioning via possible pre-army, Vietnam and homecoming pathways. Method: The Australian Vietnam Veterans' Health Study gathered data on a sample of 641 veterans throughout Australia drawn randomly from army Vietnam tour lists of the era. The data arose from interview and army records of the era, and fall into four temporal categories: pre-army, Vietnam service, homecoming after Vietnam, and current state. Path analysis models of the veterans' current psychological morbidities and social wellbeing are used to identify direct aetiological influences of earlier era constructs on current state, free of confounding by indirect (often selection) effects. Results: Our results indicate that psychological morbidity (particularly post-traumatic stress disorder) is largely influenced by combat and poor homecoming experiences, although pre-military characteristics do play some direct roles in symptomatology. Social dysfunction measures show smaller effects of the Vietnam War, which may be accounted for by an indirect association with Vietnam-related psychological morbidity. Some social measures show evidence of compensatory influences of combat, high combat leading to social dysfunction because of morbidity, but simultaneously being associated with healthier social disposition (possibly because of increased ex-service activity). Conclusions: For Australian Vietnam veterans, combat-related and homecoming effects persist on a range of psychosocial endpoints 20–30 years after exposure. These effects are not explicable in terms of veterans' pre-Vietnam characteristics.


2014 ◽  
Vol 133 ◽  
pp. 56-65 ◽  
Author(s):  
Sang-Wook Yi ◽  
Jae-Seok Hong ◽  
Heechoul Ohrr ◽  
Jee-Jeon Yi

2014 ◽  
Vol 43 (6) ◽  
pp. 1825-1834 ◽  
Author(s):  
Sang-Wook Yi ◽  
So-Yeon Ryu ◽  
Heechoul Ohrr ◽  
Jae-Seok Hong

2018 ◽  
pp. 1-3

Agent Orange was a powerful herbicide mixture used by U.S. military forces during the Vietnam War to eliminate forest cover protecting enemy troops. Much of Agent Orange contained a dangerous chemical contaminant called dioxin. An important dioxin-mediated effect on humans is causing endothelial dysfunction. If endothelium is dysfunctional and not producing normal amounts of nitric oxide, premature atherosclerosis can occur and progress. The Veterans Administration has acknowledged that Agent Orange is a risk factor for coronary artery disease. When seeing patients, it is important to determine if they served in Vietnam during the period of Agent Orange spraying. It is recommended these Veterans have aggressive coronary risk factor modification with long-term followup.


Risks ◽  
2018 ◽  
Vol 6 (3) ◽  
pp. 74 ◽  
Author(s):  
Fabiana Gómez ◽  
Jorge Ponce

This paper provides a rationale for the macro-prudential regulation of insurance companies, where capital requirements increase in their contribution to systemic risk. In the absence of systemic risk, the formal model in this paper predicts that optimal regulation may be implemented by capital regulation (similar to that observed in practice, e.g., Solvency II ) and by actuarially fair technical reserve. However, these instruments are not sufficient when insurance companies are exposed to systemic risk: prudential regulation should also add a systemic component to capital requirements that is non-decreasing in the firm’s exposure to systemic risk. Implementing the optimal policy implies separating insurance firms into two categories according to their exposure to systemic risk: those with relatively low exposure should be eligible for bailouts, while those with high exposure should not benefit from public support if a systemic event occurs.


2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Chiara Moccia ◽  
Maja Popovic ◽  
Elena Isaevska ◽  
Valentina Fiano ◽  
Morena Trevisan ◽  
...  

Abstract Background Low birthweight has been repeatedly associated with long-term adverse health outcomes and many non-communicable diseases. Our aim was to look-up cord blood birthweight-associated CpG sites identified by the PACE Consortium in infant saliva, and to explore saliva-specific DNA methylation signatures of birthweight. Methods DNA methylation was assessed using Infinium HumanMethylation450K array in 135 saliva samples collected from children of the NINFEA birth cohort at an average age of 10.8 (range 7–17) months. The association analyses between birthweight and DNA methylation variations were carried out using robust linear regression models both in the exploratory EWAS analyses and in the look-up of the PACE findings in infant saliva. Results None of the cord blood birthweight-associated CpGs identified by the PACE Consortium was associated with birthweight when analysed in infant saliva. In saliva EWAS analyses, considering a false discovery rate p-values < 0.05, birthweight as continuous variable was associated with DNA methylation in 44 CpG sites; being born small for gestational age (SGA, lower 10th percentile of birthweight for gestational age according to WHO reference charts) was associated with DNA methylation in 44 CpGs, with only one overlapping CpG between the two analyses. Despite no overlap with PACE results at the CpG level, two of the top saliva birthweight CpGs mapped at genes associated with birthweight with the same direction of the effect also in the PACE Consortium (MACROD1 and RPTOR). Conclusion Our study provides an indication of the birthweight and SGA epigenetic salivary signatures in children around 10 months of age. DNA methylation signatures in cord blood may not be comparable with saliva DNA methylation signatures at about 10 months of age, suggesting that the birthweight epigenetic marks are likely time and tissue specific.


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S319-S319
Author(s):  
Jessica Howard-Anderson ◽  
Carly Adams ◽  
Amy C Sherman ◽  
William C Dube ◽  
Teresa C Smith ◽  
...  

Abstract Background Healthcare personnel (HCP) may be at increased risk for COVID-19, but differences in risk by work activities are poorly defined. Centers for Disease Control and Prevention recommends cohorting hospitalized patients with COVID-19 to reduce in-hospital transmission of SARS-CoV-2, but it is unknown if occupational and non-occupational behaviors differ based on exposure to COVID-19 units. Methods We analyzed a subset of HCP from an ongoing CDC-funded SARS-CoV-2 serosurveillance study. HCP were recruited from four Atlanta hospitals of different sizes and patient populations. All HCP completed a baseline REDCap survey. We used logistic regression to compare occupational activities and infection prevention practices among HCP stratified by exposure to COVID-19 units: low (0% of shifts), medium (1–49% of shifts) or high (≥50% of shifts). Results Of 211 HCP enrolled (36% emergency department [ED] providers, 35% inpatient RNs, 17% inpatient MDs/APPs, 7% radiology technicians and 6% respiratory therapists [RTs]), the majority (79%) were female and the median age was 35 years. Nearly half of the inpatient MD/APPs (46%) and RNs (47%) and over two-thirds of the RTs (67%) worked primarily in the ICU. Aerosol generating procedures were common among RNs, MD/APPs, and RTs (26–58% performed ≥1), but rare among ED providers (0–13% performed ≥1). Compared to HCP with low exposure to COVID-19 units, those with medium or high exposure spent a similar proportion of shifts directly at the bedside and were about as likely to practice universal masking. Being able to consistently social distance from co-workers was rare (33%); HCP with high exposure to COVID-19 units were less likely to report social distancing in the workplace compared to those with low exposure; however, this was not significantly different (OR 0.6; 95% CI: 0.3, 1.1). Concerns about personal protective equipment in COVID-19 units were similar across levels of exposure (Table 1). Table 1: Occupational activities and infection prevention behaviors of healthcare personnel stratified by level of exposure to COVID-19 units Conclusion The proportion of time spent in dedicated COVID-19 units did not appear to influence time HCP spend directly at the bedside or infection prevention practices (social distancing and universal masking) in the workplace. Risk for SARS-CoV-2 infection in HCP may depend more on factors acting at the individual level rather than those related to location of work. Disclosures Jessica Howard-Anderson, MD, Antibacterial Resistance Leadership Group (ARLG) (Other Financial or Material Support, The ARLG fellowship provides salary support for ID fellowship and mentored research training) Ben Lopman, PhD, MSc, Takeda Pharmaceuticals (Advisor or Review Panel member, Research Grant or Support, Other Financial or Material Support, Personal fees)World Health Organization (Advisor or Review Panel member, Other Financial or Material Support, Personal fees for technical advice and analysis)


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