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

2018 ◽  
pp. 59-66
Author(s):  
Thanh Tin Nguyen ◽  
Phan Minh Triet Le ◽  
Viet Nhan Nguyen ◽  
Cristina Giuliani ◽  
Donata Luiselli ◽  
...  

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

Author(s):  
Mai Mahmoud Shaker ◽  
Taghreed Abdelmoniem shalabi ◽  
Khalda said Amr

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.


2021 ◽  
Author(s):  
Tiantian Wang ◽  
Fei Wang ◽  
Tingting Liu ◽  
Menghu Sun ◽  
Feimeng An ◽  
...  

Abstract Background and purpose: Alcohol-induced osteonecrosis of the femoral head (ONFH) is a complex and heterogeneous disease. Genetic factors and epigenetic modifications are one of the pathogenesis of the disease. However, the influence of epigenetic factors on the disease has not been systematically studied. Our research aims to determine the methylation changes of alcohol-induced ONFH.Methods:An analytical cross-sectional study of a Chinese male population (50 lung cancer patients and 50 controls). The EpiTYPER of the Sequenom MassARRAY platform was used to detect the DNA methylation status of 132 Cytosine-phosphate-Guanine (CpG) sites in the OPG/RANKL/RANK gene promoter region.Results: In the whole study group,Chi-square test was used to analyze the methylation rate between the two groups, and six CpG sites were found to be different, among which OPG1_CpG_2, OPG3_CpG_4, RANK1_CpG_6, RANK3_CpG_10, RANKL2_CpG_21, and RANKL2_CpG_46 in the case group were higher than those in the control group, while OPG4_CpG_2 was lower than that in the control group. Our results showed that 146 CpG sites were measured, of which 32 were undetectable, and of the remaining 114 methylation sites, methylation levels were different in 23 CpG sites in patients with alcohol-induced ONFH compared to healthy controls. Receiver operator characteristic (ROC) curve analysis demonstrated the methylation levels of OPG/RANKL/RANK could efficiently predict the existence of alcohol-induced ONFH.Conclusion: Our study of Chinese men suggests that several CpG sites in the OPG/RANKL/RANK gene in peripheral blood leukocytes of patients with alcohol-induced ONFH are in abnormal methylation state(hypermethylation tended to be more frequent).


2003 ◽  
Vol 49 (8) ◽  
pp. 1292-1296 ◽  
Author(s):  
Rita Castro ◽  
Isabel Rivera ◽  
Eduard A Struys ◽  
Erwin E W Jansen ◽  
Paula Ravasco ◽  
...  

Abstract Background: The pathogenic mechanism of homocysteine’s effect on cardiovascular risk is poorly understood. Recent studies show that DNA hypomethylation induced by increases in S-adenosylhomocysteine (AdoHcy), an intermediate of Hcy metabolism and a potent inhibitor of methyltransferases, may be involved in homocysteine-related pathology. Methods: We measured fasting plasma total Hcy (tHcy), AdoHcy, and S-adenosylmethionine (AdoMet) and methylation in leukocytes in 17 patients with vascular disease and in 15 healthy, age- and sex-matched controls. Results: Patient with vascular disease had significantly higher plasma tHcy and AdoHcy concentrations and significantly lower plasma AdoMet/AdoHcy ratios and genomic DNA methylation. AdoMet concentrations were not significantly different between the two groups. More than 50% of the patients fell into the highest quartiles of plasma tHcy, AdoHcy, and [3H]dCTP incorporation/μg of DNA (meaning the lowest quartile of DNA methylation status) and into the lowest quartile of the AdoMet/AdoHcy ratios of the control group. Plasma tHcy was significantly correlated with plasma AdoHcy and AdoMet/AdoHcy ratios (n = 32; P &lt; 0.001). DNA methylation status was significantly correlated with plasma tHcy and AdoHcy (n = 32; P &lt; 0.01) but not with plasma AdoMet/AdoHcy ratios. Conclusion: Global DNA methylation may be altered in vascular disease, with a concomitant increase in plasma tHcy and AdoHcy.


Author(s):  
Shan Xu ◽  
Qianping Shi ◽  
Bo Li ◽  
Liyuan Han ◽  
Guodong Xu ◽  
...  

The MTHFR gene encodes methylenetetrahydrofolate reductase required for the metabolism of homocysteine (Hcy) – a previously reported independent risk factor for ischemic stroke (IS). In this study, we first aimed to clarify the association between DNA methylation levels in the MTHFR promoter and the risk of IS, followed by the analysis of potential interactions between environmental factors and DNA methylation levels that affect IS risk. We recruited 164 patients with hypertension and IS (case group) and 345 age- and sex-matched patients with hypertension only (control group). Demographic and clinical information was obtained using questionnaires, and blood samples were collected for biochemical analyses. Fluorescence quantitative methylation-specific PCR (qMSP) was used to detect MTHFR promoter methylation levels. A logistic regression analysis was performed to determine the relationship between environmental factors, MTHFR promoter methylation levels, and IS risk. We finally generated a receiver operating characteristic (ROC) curve to determine whether MTHFR promoter methylation levels can predict IS. The mean MTHFR methylation levels in case group (8.10 ± 6.14) were significantly lower than those in control group (17.44 ± 3.16; p < 0.05). MTHFR promoter methylation levels were also lower in patients with plasma Hcy levels ≥15 μmol/L (10.65 ± 4.05) than in those with Hcy levels <15 μmol/L (16.74 ± 4.26, p < 0.001). Finally, we found that MTHFR hypermethylation is a protective factor for IS, particular in men (OR in men: 0.07; 95% CI: 0.02–0.16; p < 0.001). Further, sex and MTHFR promoter methylation levels exhibited a preliminary interaction effect on IS risk. These results indicate that MTHFR promoter methylation status might have diagnostic value in IS.


2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Tiantian Wang ◽  
Fei Wang ◽  
Tingting Liu ◽  
Menghu Sun ◽  
Feimeng An ◽  
...  

Abstract Background and purpose Alcohol-induced osteonecrosis of the femoral head (ONFH) is a complex and heterogeneous disease. Genetic factors and epigenetic modifications are one of the pathogenesis of the disease. However, the influence of epigenetic factors on the disease has not been systematically studied. Our research aims to determine the methylation changes of alcohol-induced ONFH. Methods An analytical cross-sectional study of a Chinese male population (50 alcohol-induced ONFH patients and 50 controls). The EpiTYPER of the Sequenom MassARRAY platform was used to detect the DNA methylation status of 132 cytosine-phosphate-guanine (CpG) sites in the OPG/RANKL/RANK gene promoter region. Results In the whole study group, the chi-square test was used to analyze the methylation rate between the two groups, and six CpG sites were found to be different, among which OPG1_CpG_2, OPG3_CpG_4, RANK1_CpG_6, RANK3_CpG_10, RANKL2_CpG_21, and RANKL2_CpG_46 in the case group were higher than those in the control group, while OPG4_CpG_2 was lower than that in the control group. The results showed that in patients with alcohol-induced ONFH, 146 CpG sites were examined for differences in methylation levels compared with healthy controls, 32 of which were not detected, and 23 of the remaining 114 sites showed differences in methylation levels compared with alcohol-induced ONFH patients. Receiver operator characteristic (ROC) curve analysis demonstrated the methylation levels of OPG/RANKL/RANK could efficiently predict the existence of alcohol-induced ONFH. Conclusion Our study of Chinese men suggests that several CpG sites in the OPG/RANKL/RANK gene in peripheral blood leukocytes of patients with alcohol-induced ONFH are in an abnormal methylation state (hypermethylation tended to be more frequent).


2019 ◽  
Vol 19 (6) ◽  
pp. 803-808 ◽  
Author(s):  
Luigi Vimercati ◽  
Luigi De Maria ◽  
Francesca Mansi ◽  
Antonio Caputi ◽  
Giovanni M. Ferri ◽  
...  

Background: Thyroid diseases occur more frequently in people exposed to ionizing radiation, but the relationship between occupational exposure to ionizing radiation and thyroid pathologies still remains unclear. Objective: To evaluate the prevalence of thyroid diseases in healthcare workers exposed to low-level ionizing radiation compared with a control group working at the University Hospital of Bari, Southern Italy, and living in the same geographical area, characterized by mild iodine deficiency. Methods: We ran a cross-sectional study to investigate whether healthcare workers exposed to ionizing radiation had a higher prevalence of thyroid diseases. Four hundred and forty-four exposed healthcare workers (241 more exposed, or “A Category”, and 203 less exposed, or “B Category”) and 614 nonexposed healthcare workers were enrolled during a routine examination at the Occupational Health Unit. They were asked to fill in an anamnestic questionnaire and undergo a physical examination, serum determination of fT3, fT4 and TSH, anti-TPO ab and anti-TG ab and ultrasound neck scan. Thyroid nodules were submitted to fine needle aspiration biopsy when indicated. Results: The prevalence of thyroid diseases was statistically higher in the exposed workers compared to controls (40% vs 29%, adPR 1.65; IC95% 1.34-2.07). In particular, the thyroid nodularity prevalence in the exposed group was approximately twice as high as that in the controls (29% vs 13%; adPR 2.83; IC95% 2.12-3.8). No statistically significant association was found between exposure to ionizing radiation and other thyroid diseases. Conclusion: In our study, mild ionizing radiation-exposed healthcare workers had a statistically higher prevalence of thyroid diseases than the control group. The results are likely due to a closer and more meticulous health surveillance programme carried out in the ionising radiation-exposed workers, allowing them to identify thyroid alterations earlier than non-exposed health staff.


Genes ◽  
2021 ◽  
Vol 12 (5) ◽  
pp. 680
Author(s):  
Rujuan Dai ◽  
Zhuang Wang ◽  
S. Ansar Ahmed

Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease that afflicts multiple organs, especially kidneys and joints. In addition to genetic predisposition, it is now evident that DNA methylation and microRNAs (miRNAs), the two major epigenetic modifications, are critically involved in the pathogenesis of SLE. DNA methylation regulates promoter accessibility and gene expression at the transcriptional level by adding a methyl group to 5′ cytosine within a CpG dinucleotide. Extensive evidence now supports the importance of DNA hypomethylation in SLE etiology. miRNAs are small, non-protein coding RNAs that play a critical role in the regulation of genome expression. Various studies have identified the signature lupus-related miRNAs and their functional contribution to lupus incidence and progression. In this review, the mutual interaction between DNA methylation and miRNAs regulation in SLE is discussed. Some lupus-associated miRNAs regulate DNA methylation status by targeting the DNA methylation enzymes or methylation pathway-related proteins. On the other hand, DNA hyper- and hypo-methylation are linked with dysregulated miRNAs expression in lupus. Further, we specifically discuss the genetic imprinting Dlk1-Dio3 miRNAs that are subjected to DNA methylation regulation and are dysregulated in several autoimmune diseases, including SLE.


2018 ◽  
Vol 44 (1) ◽  
pp. 31-35 ◽  
Author(s):  
Martín Bedolla-Barajas ◽  
Norma Angélica Pulido-Guillén ◽  
Bolívar Vivar-Aburto ◽  
Jaime Morales-Romero ◽  
José Raúl Ortiz-Peregrina ◽  
...  

ABSTRACT Objective: To investigate whether there is an association between suicidal ideation (SI) and allergic diseases in adults. Methods: This was a comparative cross-sectional study involving individuals ranging from 20 to 50 years of age recruited from a university hospital in the city of Guadalajara, Mexico. We included patients with a confirmed diagnosis of allergic asthma, those with a confirmed diagnosis of allergic rhinitis, and healthy controls. All subjects completed the Beck Depression Inventory-II (BDI-II), which includes an item that evaluates the presence of suicidal thoughts or desires within the last two weeks, in order to identify SI. Results: The sample comprised 115 patients with allergic asthma, 111 patients with allergic rhinitis, and 96 healthy controls. The number of individuals identified with SI in the three groups were, respectively, 17 (14.8%), 13 (11.7%), and 8 (8.3%). Regarding the presence of SI, no statistically significant association was found in the allergic asthma group (OR = 1.98; 95% CI: 0.78-4.64; p = 0.154) or in the allergic rhinitis group (OR = 1.46; 95% CI: 0.58-3.68; p = 0.424) when they were compared with the control group. However, the presence of depression was associated with SI in the three groups: allergic asthma (OR = 12.36; 95% CI: 2.67-57.15; p = 0.001); allergic rhinitis (OR = 6.20; 95% CI: 1.66-23.14; p = 0.006); and control (OR = 21.0; 95% CI: 3.75-117.36; p < 0,001). Conclusions: In comparison with the control group, no association was found between SI and the groups with allergic diseases. In contrast, there was association between SI and depression in the three groups.


2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Fatma Al Hoqani ◽  
Wadha Al Ghafri ◽  
Saneya El tayeb ◽  
Yahya Al Farsi ◽  
Vaidyanathan Gowri

Objective: to determine the prevalence of explained and unexplained recurrent miscarriages (RM) and to find out if there is a significant relationship between recurrent miscarriages and consanguinity. Methods: A cross sectional in which the cases group included all women with RM attending the outpatient clinic at Sultan Qaboos University Hospital from July 2006 to April 2012 and the controls group included women with no history of RM after matching them with cases for age (case to control ratio was 1:1). The main outcome measures were the prevalence of consanguinity in women with or without recurrent miscarriages. Results: During study period a total of 290 women with RM were seen. Of which, 150 (51.7%) women had unexplained RM. Control group with no history of RM were 300 women. Consanguinity rate among cases (49.5%) %) was less than the controls (52.7 %%). Both first cousin and second cousin marriages were more common in the controls than the cases and it was not statistically significant (p value 0.476, chi squared test). Conclusion: In this study we found that more than half of RM cases were unexplained and there was no significant association between RM and consanguinity.


Author(s):  
Suryani Jamal ◽  
Uleng Bahrun ◽  
Ibrahim Abdul Samad ◽  
Fitriani Mangarengi ◽  
Hasyim Kasim ◽  
...  

This study aimed to analyze endocan levels as a marker of endothelial dysfunction in the control group, patients withstage I hypertension, stage II hypertension, and patients with end-stage renal disease. Endocan levels were measured withESM-1 (endocan) kit by Enzyme-Linked Immunosorbent Assay (ELISA) method. This study used a cross-sectional methodand was conducted in Dr. Wahidin Sudirohusodo Hospital, Makassar and Hasanuddin University Hospital from Septemberto October 2017. There were 83 samples in this study, consisting of 12 samples in the control group, 22 samples of stage Ihypertension, 28 samples of stage II hypertension, and 21 samples of end-stage renal disease aged 20-90 years old. Thisstudy showed significantly higher endocan levels in patients with stage II hypertension and end-stage renal disease(p< 0.05). Endocan levels were significantly higher (p<0.05) in patients with end-stage renal disease compared with thecontrol group and patients with stage I hypertension; but not significantly higher (p > 0.05) compared to patients with stageII hypertension. Also, the median of endocan levels in patients with the end-stage renal disease was higher (309,850 ng/L)compared to patients with stage II hypertension (273,050 ng/L).


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