The effect of DNA methylation on bumblebee colony development

Abstract Background Although around 1% of cytosines in bees’ genomes are known to be methylated, less is known about methylation’s effect on bee behavior and fitness. Chemically altered DNA methylation levels have shown clear changes in the dominance and reproductive behavior of workers in queen-less colonies, but the global effect of DNA methylation on caste determination and colony development remains unclear, mainly because of difficulties in controlling for genetic differences among experimental subjects in the parental line. Here, we investigated the effect of the methylation altering agent decitabine on the developmental rate of full bumblebee colonies. Whole genome bisulfite sequencing was used to assess differences in methylation status. Results Our results showed fewer methylated loci in the control group. A total of 22 CpG loci were identified as significantly differentially methylated between treated and control workers with a change in methylation levels of 10% or more. Loci that were methylated differentially between groups participated in pathways including neuron function, oocyte regulation and metabolic processes. Treated colonies tended to develop faster, and therefore more workers were found at a given developmental stage. However, male production followed the opposite trend and it tended to be higher in control colonies. Conclusion Overall, our results indicate that altered methylation patterns resulted in an improved cooperation between workers, while there were no signs of abnormal worker dominance or caste determination.

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P1052EXPANDED HEMODIALYSIS (HDX) DOES NOT AFFECT EPIGENETIC INTERCELLULAR SIGNALS INVOLVED IN INFLAMMATION AND CARDIOVASCULAR DISEASE

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p1052 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Carmen Vida ◽

Matilde Alique ◽

Patricia De Sequera Ortiz ◽

Guillermo Bodega ◽

Carlos Oliva ◽

...

Keyword(s):

Dna Methylation ◽

Methylation Status ◽

Control Group ◽

Dialysis Session ◽

Plasma Dna ◽

Methylated Dna ◽

Dna And Rna ◽

Before And After ◽

Dialysis Membranes ◽

And Control

Abstract Background and Aims Epigenetic signals play a principal role in homeostasis, but also may promote diseases including cardiovascular diseases (CVDs) when are altered. Extracellular vesicles (EVs) or plasma circulating DNA and RNA may have relevant functions in both physiological and pathophysiological contexts related to the epigenetic intercellular communication. Thus, changes in the endothelial or platelet EVs, or the plasma circulating methylated DNA may contribute to the chronic inflammation and the subsequent CVDs in chronic kidney disease patients, particularly when are in hemodialysis (HD). Dialysis membranes do not usually allow the passage of molecules larger than 30-40 kDa. However, the new system of expanded hemodialysis (HDx) with a medium-cut-off membrane (MCO), due to its characteristics, could alter the plasma content of these EVs and DNA methylation, and thereby, promote the development of CVDs. Therefore, our study evaluates whether global plasma DNA methylation and EVs content are modified during an HDx session. Method For this study, we selected 12 dialysis patients: HDx patients (n=6; dialyzed with MCO) and control group (n=6; dialyzed with other HD membranes). Before and after a dialysis session, plasma samples were obtained. EVs were isolated by ultracentrifugation, and the total number of EVs and platelet and endothelial-derived EVs were characterized and quantified by flow cytometry. RNA and DNA extraction and quantification were carried out using different kits and NanoDrop spectrophotometer. DNA methylation was assessed with a 5-methyl cytosine (5-mC) DNA assay kit. Results As shown in the figure, after a dialysis session with the HDx, no significant differences were observed in the total number of EVs, as well in the number of platelet- and endothelial-derived EVs, in comparison to those observed in HDx patients before the dialysis session. By contrast, patients dialyzed with other HD membranes presented differences in the number of total EVs and platelet and endothelial EVs, which decreased significantly (p<0.05) after the dialysis session. Concerning DNA methylation, no statistically significant changes in total DNA 5-mC (%) were observed in both HDx and control patients after the dialysis session. However, a slight tendency to decrease methylated DNA was observed with the HDx compared to other HD membranes (control). Moreover, no significant changes in DNA and RNA % were observed after dialysis session in both HDx and control group. Conclusion To our knowledge, this is the first study to investigate the influence of the HDx technique on the content of plasma cellular EVs and DNA methylation status. HDx does not affect EVs levels, although it shows a tendency to purify plasma methylated DNA. Although this study was not designed to analyze the comparative effectiveness between different membranes, interestingly this effect in epigenetic signals was not observed with other HD membranes, where patients showed a marked reduction of EVs content. The differential activity of HDx about other HD membranes deserves further investigation. Funding (PI17/01029; PI19/00240; ISCIII-FEDER). Santander/UCM PR41/17-20964. Spanish Society of Nephrology 2018. UAH-GP2018-4

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Correlation of methylation status in MTHFR promoter region with recurrent pregnancy loss

Journal of Genetic Engineering and Biotechnology ◽

10.1186/s43141-021-00147-w ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Mai Mahmoud Shaker ◽

Taghreed Abdelmoniem shalabi ◽

Khalda said Amr

Keyword(s):

Dna Methylation ◽

Dna Sequences ◽

Promoter Region ◽

Pregnancy Loss ◽

Recurrent Pregnancy Loss ◽

Methylation Status ◽

Control Group ◽

Case Group ◽

Methyl Radical ◽

Fertile Women

Abstract Background DNA methylation is an epigenetic process for modifying transcription factors in various genes. Methylenetetrahydrofolate reductase (MTHFR) stimulates synthesis of methyl radical in the homocysteine cycle and delivers methyl groups needed in DNA methylation. Furthermore, numerous studies have linked gene polymorphisms of this enzyme with a larger risk of recurrent pregnancy loss (RPL), yet scarce information is available concerning the association between epigenetic deviations in this gene and RPL. Hypermethylation at precise DNA sequences can function as biomarkers for a diversity of diseases. We aimed by this study to evaluate the methylation status of the promoter region of MTHFR gene in women with RPL compared to healthy fertile women. It is a case–control study. Hundred RPL patients and hundred healthy fertile women with no history of RPL as controls were recruited. MTHFR C677T was assessed by polymerase chain reaction-restriction fragment length polymorphism (RFLP). Quantitative evaluation of DNA methylation was performed by high-resolution melt analysis by real-time PCR. Results The median of percentage of MTHFR promoter methylation in RPL cases was 6.45 [0.74–100] vs. controls was 4.50 [0.60–91.7], P value < 0.001. In the case group, 57 hypermethylated and 43 normo-methylated among RPL patients vs. 40 hypermethylated and 60 normo-methylated among controls, P< 0.005. Frequency of T allele in C677T MTHFR gene among RPL patients was 29% vs. 23% among the control group; C allele vs. T allele: odds ratio (OR) = 1.367 (95% confidence interval (CI) 0.725–2.581). Conclusion Findings suggested a significant association between hypermethylation of the MTHFR promoter region in RPL patients compared to healthy fertile women.

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Regulation of adenosine A2Areceptor gene expression in a model of binge eating in the amygdaloid complex of female rats

Journal of Psychopharmacology ◽

10.1177/0269881119845798 ◽

2019 ◽

Vol 33 (12) ◽

pp. 1550-1561 ◽

Cited By ~ 12

Author(s):

Maria Vittoria Micioni Di Bonaventura ◽

Mariangela Pucci ◽

Maria Elena Giusepponi ◽

Adele Romano ◽

Catia Lambertucci ◽

...

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Binge Eating ◽

Epigenetic Regulation ◽

Methylation Status ◽

Amygdaloid Complex ◽

Female Rats ◽

Control Group ◽

Compensatory Mechanism ◽

Mrna Levels

Background:Pharmacological treatment approaches for eating disorders, such as binge eating disorder and bulimia nervosa, are currently limited.Methods and aims:Using a well-characterized animal model of binge eating, we investigated the epigenetic regulation of the A2AAdenosine Receptor (A2AAR) and dopaminergic D2 receptor (D2R) genes.Results:Gene expression analysis revealed a selective increase of both receptor mRNAs in the amygdaloid complex of stressed and restricted rats, which exhibited binge-like eating, when compared to non-stressed and non-restricted rats. Consistently, pyrosequencing analysis revealed a significant reduction of the percentage of DNA methylation but only at the A2AAR promoter region in rats showing binge-like behaviour compared to the control animals. Focusing thus on A2AAR agonist (VT 7) administration (which inhibited the episode of binge systemically at 0.1 mg/kg or intra-central amygdala (CeA) injection at 900 ng/side) induced a significant increase of A2AAR mRNA levels in restricted and stressed rats when compared to the control group. In addition, we observed a significant decrease in A2AAR mRNA levels in rats treated with the A2AAR antagonist (ANR 94) at 1 mg/kg. Consistent changes in the DNA methylation status of the A2AAR promoter were found in restricted and stressed rats after administration of VT 7 or ANR 94.Conclusion:We confirm the role of A2AAR in binge eating behaviours, and we underline the importance of epigenetic regulation of the A2AAR gene, possibly due to a compensatory mechanism to counteract the effect of binge eating. We suggest that A2AAR activation, inducing receptor gene up-regulation, could be relevant to reduction of food consumption.

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Investigating skewness to understand gene expression heterogeneity in large patient cohorts

BMC Bioinformatics ◽

10.1186/s12859-019-3252-0 ◽

2019 ◽

Vol 20 (S24) ◽

Cited By ~ 2

Author(s):

Benjamin V. Church ◽

Henry T. Williams ◽

Jessica C. Mar

Keyword(s):

Dna Methylation ◽

Methylation Status ◽

Microarray Technology ◽

Statistical Measure ◽

Large Patient ◽

Technology Platforms ◽

Gene Expression Heterogeneity ◽

Cancer Genome Atlas ◽

Or Genes ◽

And Control

Abstract Background Skewness is an under-utilized statistical measure that captures the degree of asymmetry in the distribution of any dataset. This study applied a new metric based on skewness to identify regulators or genes that have outlier expression in large patient cohorts. Results We investigated whether specific patterns of skewed expression were related to the enrichment of biological pathways or genomic properties like DNA methylation status. Our study used publicly available datasets that were generated using both RNA-sequencing and microarray technology platforms. For comparison, the datasets selected for this study also included different samples derived from control donors and cancer patients. When comparing the shift in expression skewness between cancer and control datasets, we observed an enrichment of pathways related to the immune function that reflects an increase towards positive skewness in the cancer relative to control datasets. A significant correlation was also detected between expression skewness and the top 500 genes corresponding to the most significant differential DNA methylation occurring in the promotor regions for four Cancer Genome Atlas cancer cohorts. Conclusions Our results indicate that expression skewness can reveal new insights into transcription based on outlier and asymmetrical behaviour in large patient cohorts.

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72 EFFECT OF CELL CYCLE PHASE OF GENE-MANIPULATED FETAL FIBROBLASTS ON THE DEVELOPMENT OF CLONED BOVINE EMBRYOS

Reproduction Fertility and Development ◽

10.1071/rdv17n2ab72 ◽

2005 ◽

Vol 17 (2) ◽

pp. 186

Author(s):

M. Urakawa ◽

T. Sawada ◽

Y. Sendai ◽

Y. Shinkai ◽

A. Ideta ◽

...

Keyword(s):

Cell Cycle ◽

Donor Cell ◽

Developmental Rate ◽

G1 Phase ◽

Control Group ◽

Rate Of Development ◽

Normal Fetus ◽

Fetal Fibroblasts ◽

Blastocyst Rate ◽

And Control

Transgenic bovine fetuses and offspring can be produced by using gene-modified somatic cells and clones of these cells. In this study, we examined the effects of specific cell cycle (early G1 phase) of donor cell (gene-manipulated fibroblasts) on the development of the nuclear transfer (NT) embryos into blastocysts and on the fetus production after embryo transfer. The gene-manipulated (tg; targeting of one or both alleles of gene encoding α-1,3-galactosyltransferase) or non-manipulated (control) bovine fetal fibroblasts were used for NT. The fibroblasts transfected with the targeting vector were selected with 0.4 mg mL−1 G418. The G418-resistant cells were monitored by PCR and Southern blot analysis. The cells (tg cells) in which homologous recombination occurred were used for NT. For NT, both tg cells and control cells were cultured in DMEM with 10% FCS. Early G1 cells were prepared by choosing pairs of bridged cells derived from mitotic phase cells (Urakawa M et al. 2004 Theriogenology 62, 714–728), and non-synchronized cells were obtained from a culture plate that had reached 60–80% confluence. Each donor cell was inserted into an enucleated, in vitro-matured (19 h) oocyte. Oocyte-cell couples were electrofused and activated with calcium ionophore and cycloheximide. The NT embryos were then co-cultured with bovine oviduct epithelial cells in CR1aa with 5% CS. The blastocyst rates were determined at 6 days after NT. The blastocysts were nonsurgically transferred to recipient heifers, and the developmental rate to the normal fetus was examined by the recovery of fetus or by using ultrasonography at Days 35–42. Data were analyzed by ANOVA. The developmental rate to the blastocyst stage did not differ significantly between tg (28.4%, 128/425) and control (25.4%, 181/739) cell groups. In the control group, the blastocyst rate of embryos constructed from early G1 phase fibroblasts (25.7%, 80/311) was not significantly different from that of embryos constructed with non-synchronized fibroblasts (23.6%, 101/428). In contrast, the blastocyst rate of tg cell derived-embryos was lower (P < 0.05) in early G1 phase (23.5%, 71/302) than in non-synchronized cell phase (46.3%, 57/123). The rate of development to a normal fetus in the tg group (15.4%, 4/26) was significant lower than that in the control group (62.5%, 25/40). For both the tg group and the control group, the rate of development to fetus tended to be higher (P > 0.05) for blastocysts derived from cells at the early G1 phase than for blastocysts derived from non-synchronized cells (tg group, 25.0%, 3/12 v. 7.1%, 1/14; control group, 90.0%, 9/10 v. 53.3%, 16/30). These results demonstrate that gene modification of fetal fibroblasts affects the development of NT embryos to fetuses. In addition, the synchronization of genetically modified donor cells to the early G1 phase may increase the potential to develop to a normal fetus.

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DNA Methylation Changes and Its Associated Genes in Mulberry (Morus alba L.) Yu-711 Response to Drought Stress Using MethylRAD Sequencing

Plants ◽

10.3390/plants11020190 ◽

2022 ◽

Vol 11 (2) ◽

pp. 190

Author(s):

Michael Ackah ◽

Liangliang Guo ◽

Shaocong Li ◽

Xin Jin ◽

Charles Asakiya ◽

...

Keyword(s):

Dna Methylation ◽

Gene Regulation ◽

Drought Stress ◽

Methylation Status ◽

Enrichment Analysis ◽

Plant Genome ◽

Pcr Analysis ◽

Kegg Pathways ◽

Wide Range ◽

And Control

Drought stress remains one of the most detrimental environmental cues affecting plant growth and survival. In this work, the DNA methylome changes in mulberry leaves under drought stress (EG) and control (CK) and their impact on gene regulation were investigated by MethylRAD sequencing. The results show 138,464 (37.37%) and 56,241 (28.81%) methylation at the CG and CWG sites (W = A or T), respectively, in the mulberry genome between drought stress and control. The distribution of the methylome was prevalent in the intergenic, exonic, intronic and downstream regions of the mulberry plant genome. In addition, we discovered 170 DMGs (129 in CG sites and 41 in CWG sites) and 581 DMS (413 in CG sites and 168 in CWG sites). Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicates that phenylpropanoid biosynthesis, spliceosome, amino acid biosynthesis, carbon metabolism, RNA transport, plant hormone, signal transduction pathways, and quorum sensing play a crucial role in mulberry response to drought stress. Furthermore, the qRT-PCR analysis indicates that the selected 23 genes enriched in the KEGG pathways are differentially expressed, and 86.96% of the genes share downregulated methylation and 13.04% share upregulation methylation status, indicating the complex link between DNA methylation and gene regulation. This study serves as fundamentals in discovering the epigenomic status and the pathways that will significantly enhance mulberry breeding for adaptation to a wide range of environments.

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Combination Analysis of NR3C1, MTHFR and IGFBP3 Gene Polymorphisms and DNA Methylation With Steroid-induced Osteonecrosis of the Femoral Head Risk in Chinese Han Population

10.21203/rs.3.rs-87796/v1 ◽

2020 ◽

Author(s):

Ronglan Huang ◽

Qinghao Zhan ◽

Wenbin Hu ◽

Renmin Yang ◽

Nan Cheng ◽

...

Keyword(s):

Dna Methylation ◽

Femoral Head ◽

Methylation Level ◽

Gene Polymorphisms ◽

Methylation Status ◽

Chinese Han Population ◽

Control Group ◽

Chinese Han ◽

Han Population ◽

Wide Range

Abstract Background: Although the precise etiology of osteonecrosis of the femoral head (ONFH) has yet to be fully elucidated, it is known that nuclear receptor subfamily3, group C, member 1 (NR3C1), 5, 10-methylenetetrahydrofolate reductase (MTHFR) and insulin-like growth factor-binding protein 3 (IGFBP3) are related to the pathophysiology of steroid-induced osteonecrosis of the femoral head (SONFH). The expression of NR3C1, MTHFR and IGFBP3 are regulated by epigenetics and genetic profiles. Objective: The primary objective of this study was to investigated the association between NR3C1, MTHFR and IGFBP3 gene polymorphisms and DNA methylation status and SONFH.Methods: This case-control study included 79 patients with SONFH and 114 patients who took steroids but did not develop SONFH. We evaluated 5 single-nucleotide polymorphisms (SNPs) out of 3 genes in Chinese Han population. These SNPs were genotyped by improved multiplex ligation detection reaction (iMLDR). Methyltarget was used to test the methylation level of positive sites, the interaction between SNPs and DNA methylation level was analyzed using eQTLD technique.Results: We identified rs3110697 in the IGFBP3 gene that was potentially associated with a reduced risk of SONFH in the genotype (P=0.008; odds ratio [OR]: 0.741; 95% confidence intervals [CI]: 0.456–1.205) and in the recessive model (P=0.003; OR: NA; 95% CI: NA–NA). Furthermore, CpG sites with significant differences in methylation levels were screened as follows: IGFBP3_2-143, MTHFR_1-36, MTHFR_1-77, MTHFR_1-139, MTHFR_2-42, NR3C1_2-163, NR3C1_4-47, and the differences were statistically significant compared with the control group (p<0.05). A total of 10 pairs of linear regression tests of SNP and methylation sites were statistically significant (p<0.05).Conclusions: SONFH is a polygenic disorder in which a wide range of interactions between SNPs and DNA methylation levels may dominate the course of the disease.

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Identification of DNA Methylation Changes That Predict Onset of Post-traumatic Stress Disorder and Depression Following Physical Trauma

Frontiers in Neuroscience ◽

10.3389/fnins.2021.738347 ◽

2021 ◽

Vol 15 ◽

Author(s):

Carina A. Martin ◽

Rany Vorn ◽

Martin Schrieber ◽

Chen Lai ◽

Sijung Yun ◽

...

Keyword(s):

Dna Methylation ◽

Post Traumatic Stress Disorder ◽

Traumatic Stress ◽

Stress Disorder ◽

Stressful Events ◽

Control Group ◽

Post Traumatic Stress ◽

Physical Trauma ◽

Post Traumatic ◽

And Control

Post-traumatic stress disorder (PTSD) and major depressive disorder (MDD) are commonly experienced after exposure to highly stressful events, including physical trauma, yet, biological predictors remain elusive. Methylation of DNA may provide key insights, as it likely is reflective of factors that may increase the risk in trauma patients, as DNA methylation is altered by previous stressors. Here, we compared DNA methylation patterns using bisulfite sequencing in patients with a physical trauma that required more than a 24-h hospitalization (n = 33). We then compared DNA methylation in patients who developed and compared the following groups (1) PTSD and MDD; n = 12), (2) MDD (patients with MDD only; n = 12), and (3) control (patients who did not have PTSD or MDD; n = 9), determined by the PTSD Checklist (PCL-5) and Quick Inventory of Depressive Symptomatology (QIDS) at 6-months follow-up. We identified 17 genes with hypermethylated cytosine sites and 2 genes with hypomethylated sites in comparison between PTSD and control group. In comparison between MDD and control group, we identified 12 genes with hypermethylated cytosine sites and 6 genes with hypomethylated sites. Demethylation of these genes altered the CREB signaling pathway in neurons and may represent a promising therapeutic development target for PTSD and MDD. Our findings suggest that epigenetic changes in these gene regions potentially relate to the onset and symptomology of PTSD and MDD and could be used as potential biomarkers in predicting the onset of PTSD or MDD following traumatic events.

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167 EFFECT OF DNA METHYLATION INHIBITOR ON HETEROCHROMATIN IN BOVINE EMBRYOS DERIVED FROM HEAT-SHOCKED OOCYTES

Reproduction Fertility and Development ◽

10.1071/rdv28n2ab167 ◽

2016 ◽

Vol 28 (2) ◽

pp. 213

Author(s):

T. D. Araujo ◽

J. Jasmin ◽

C. C. R. Quintao ◽

E. D. Souza ◽

J. H. M. Viana ◽

...

Keyword(s):

Dna Methylation ◽

Heat Shock ◽

In Vitro Maturation ◽

Methylation Status ◽

Control Groups ◽

Methylation Inhibitor ◽

Response To Stress ◽

Dna Methylation Inhibitor ◽

And Control

The cell response to stress involves epigenetic modifications in order to regulate the gene expression, which is dependent of chromatin structure and DNA methylation status. On the other hand, changes on DNA methylation can have an effect on chromatin organisation (Espada and Esteller 2010 Semin. Cell. Dev. Biol. 21, 238–246). In this study we evaluated the effect of 5-aza-2′-deoxycytidine (5-aza; Sigma, St. Louis, MO, USA), a DNA methylation inhibitor, on heterochromatin 1 β formation of bovine pre-implantation embryos derived from oocytes that did or did not undergo heat shock during in vitro maturation (IVM). Oocytes were IVM under 38.5°C for 24 h (non-heat-shock: NHS group) or under 41.5°C for 12 h followed by 38.5°C for 12 h (heat-shock: HS group). Oocytes were IVF for 20 h and the denuded presumptive zygotes from NHS or HS groups were cultured with 0 (nontreated controls) or 10 nM of 5-aza for 24 h or 48 h in CR2aa plus 2.5% FCS at 38.5°C with 5% CO2, 5% O2 and 90% N2. Embryos with 4–7 cells at 44 h post-insemination (hpi) and embryos with 8–16 cells at 68 hpi were fixed in 4% paraformaldehyde and stained with anti-mouse HP1β first antibody, then immunofluorescence was evaluated by confocal microscopy (Leica TCS SP5II) and images were processed by ImageJ 1.49 (NIH, Bethesda, MD, USA). Fluorescence of nuclei and of background area (fluorescence/unit area) were measured and then the corrected relative fluorescence per nucleus was calculated. We analysed 129 and 149 nuclei at 44 hpi from 29 and 34 embryos as well as 268 and 182 nuclei at 68 hpi from 37 and 22 embryos of the NHS and HS groups, respectively, obtained from 3 replicates. Data underwent log-transformation and was analysed by ANOVA, and means compared by Student-Newman-Keuls. Embryos with 8–16 cells derived from NHS oocytes and treated with 5-aza for 24 h or for 48 h had nuclei with lower HP1 fluorescence than their respective NHS (nontreated) control (P < 0.01). In contrast, 8–16-cells embryos derived from HS and treated with 5-aza displayed nuclei with the same HP1 fluorescence of their respective HS control (P > 0.05). When embryos derived from HS and NHS (nontreated) control groups were compared, higher HP1 fluorescence was found in those with 4–7 cells of HS group (P < 0.05); however, embryos with 8–16 cells displayed similar HP1 fluorescence between both NHS and HS control groups (P > 0.05). There was no difference on HP1 fluorescence between nuclei of embryos with 4–7 cells treated with 5-aza for 24 h and control (nontreated) in both HS and NHS groups. These data suggest that embryos derived from heat-shocked oocytes can accumulate more heterochromatin at earlier stages than those from non-heat-shocked oocytes and that the effect of DNA methylation inhibition by 5-aza on embryo heterochromatin can vary accordingly to the exposure of the oocyte to heat shock during in vitro maturation. Financial support from CNPq, Fapemig, and CAPES is acknowledged.

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THE DNA METHYLATION STATUS IN PRESENT DAY POPULATIONS LIVING IN AREAS OF VIETNAM SUBJECTED TO AGENT ORANGE SPRAYING DURING THE WAR IN NAM DONG AND A LUOI, THUA THIEN HUE PROVINCE

Journal of Medicine and Pharmacy ◽

10.34071/jmp.2018.2.10 ◽

2018 ◽

pp. 59-66

Author(s):

Thanh Tin Nguyen ◽

Phan Minh Triet Le ◽

Viet Nhan Nguyen ◽

Cristina Giuliani ◽

Donata Luiselli ◽

...

Keyword(s):

Dna Methylation ◽

Methylation Status ◽

University Hospital ◽

Agent Orange ◽

Control Group ◽

Case Group ◽

Veterans Health ◽

Dna Hypomethylation ◽

Cross Sectional ◽

Cyp1a1 Gene

Introduction: Agent Orange was the most extensively used among herbicides sprayed on Vietnam territory during the Vietnam War. Its by-product, 2,3,7,8-tetrachlorodibenzo-paradioxin (Dioxin), is an extremely toxic and persistent chemical. The effects of this spraying on both Vietnamese and United States Veterans health has been reported in many publications. However, there wasn’t any study of the effects at the molecular level of the residual Dioxin in the environment on present Vietnamese civilians living in contaminated areas. Objective: To investigate the association between residual Agent Orange/Dioxin in the environment and the alterations of DNA methylation in the peripheral blood of the present day Vietnamese population living in spraying areas. Methods: Cross-sectional study. The subjects were 188 individuals who came to Hue University Hospital for health care: 94 individuals for case group from sprayed areas (A Luoi and Nam Dong, Thua Thien Hue Province), and 94 individuals for the control group from non-sprayed areas (Quang Binh to North Vietnam). MALDI-TOF MS technique was used to detect the alterations of DNA methylation of CYP1A1 gene. Results: Among 22 CpG position of CYP1A1 gene were investigated, there were the DNA hypomethylation at CpG_2.3.4, CpG_5, CpG_12.13 in case group compared to the control (p<0.05). After dividing case group into 2 subgroups, we found the significant DNA hypomethylation at CpG_2.3.4, CpG_5, CpG_9, CpG_10, CpG_11, CpG_12.13, CpG_17, CpG_18.19 in subgroup CASES_F_P compared to CASES_NON_F_P also control group (p< 0.05). Conclusions: Individuals living in A Luoi and Nam Dong– the Dioxin contaminated areas– had DNA hypomethylation in CYP1A1 gene. The DNA hypomethylation seem not due to the effects of residual Dioxin in the environment in present day, it was likely to be inherited by epigenetic way from the DNA methylation alterations on their parents who had directly exposure to that spraying. This theory should be verified through extensive studies with CASES_F_P family and more genes will be investigated. Key words: Agent Orange, Dioxin, DNA methylation, CYP1A1

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