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DNA methylation signatures as biomarkers of socioeconomic position. DNA甲基化特征作为社会经济地位的生物标志物。
IF 3.8 Q1 Environmental Science Pub Date : 2022-12-14 eCollection Date: 2023-01-01 DOI: 10.1093/eep/dvac027
Meghna Rajaprakash, Lorraine T Dean, Meredith Palmore, Sara B Johnson, Joan Kaufman, Daniele M Fallin, Christine Ladd-Acosta

This review article provides a framework for the use of deoxyribonucleic acid (DNA) methylation (DNAm) biomarkers to study the biological embedding of socioeconomic position (SEP) and summarizes the latest developments in the area. It presents the emerging literature showing associations between individual- and neighborhood-level SEP exposures and DNAm across the life course. In contrast to questionnaire-based methods of assessing SEP, we suggest that DNAm biomarkers may offer an accessible metric to study questions about SEP and health outcomes, acting as a personal dosimeter of exposure. However, further work remains in standardizing SEP measures across studies and evaluating consistency across domains, tissue types, and time periods. Meta-analyses of epigenetic associations with SEP are offered as one approach to confirm the replication of DNAm loci across studies. The development of DNAm biomarkers of SEP would provide a method for examining its impact on health outcomes in a more robust way, increasing the rigor of epidemiological studies.

这篇综述文章为使用脱氧核糖核酸(DNA)甲基化(DNAm)生物标志物研究社会经济地位(SEP)的生物嵌入提供了一个框架,并总结了该领域的最新进展。它介绍了新出现的文献,显示了个人和社区水平的SEP暴露与整个生命过程中的DNAm之间的关联。与基于问卷的SEP评估方法相反,我们认为DNAm生物标志物可以作为个人暴露剂量计,为研究SEP和健康结果的问题提供一个可访问的指标。然而,在标准化各研究的SEP测量以及评估各领域、组织类型和时间段的一致性方面,仍有进一步的工作要做。表观遗传学与SEP关联的荟萃分析是确认DNAm基因座在研究中复制的一种方法。SEP的DNAm生物标志物的开发将提供一种更有力的方法来检查其对健康结果的影响,从而提高流行病学研究的严谨性。
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引用次数: 0
Environmental epigenetics and climate change. 环境表观遗传学与气候变化。
IF 3.8 Q1 Environmental Science Pub Date : 2022-12-14 eCollection Date: 2023-01-01 DOI: 10.1093/eep/dvac028
Michael K Skinner
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引用次数: 0
Duration of exposure to epidural anesthesia at delivery, DNA methylation in umbilical cord blood and their association with offspring asthma in Non-Hispanic Black women. 非西班牙裔黑人妇女分娩时硬膜外麻醉持续时间、脐带血DNA甲基化及其与后代哮喘的关系
IF 3.8 Q1 Environmental Science Pub Date : 2022-12-13 eCollection Date: 2023-01-01 DOI: 10.1093/eep/dvac026
Yaxu Wang, Jung-Ying Tzeng, Yueyang Huang, Rachel Maguire, Cathrine Hoyo, Terrence K Allen

Epidural anesthesia is an effective pain relief modality, widely used for labor analgesia. Childhood asthma is one of the commonest chronic medical illnesses in the USA which places a significant burden on the health-care system. We recently demonstrated a negative association between the duration of epidural anesthesia and the development of childhood asthma; however, the underlying molecular mechanisms still remain unclear. In this study of 127 mother-child pairs comprised of 75 Non-Hispanic Black (NHB) and 52 Non-Hispanic White (NHW) from the Newborn Epigenetic Study, we tested the hypothesis that umbilical cord blood DNA methylation mediates the association between the duration of exposure to epidural anesthesia at delivery and the development of childhood asthma and whether this differed by race/ethnicity. In the mother-child pairs of NHB ancestry, the duration of exposure to epidural anesthesia was associated with a marginally lower risk of asthma (odds ratio = 0.88, 95% confidence interval = 0.76-1.01) for each 1-h increase in exposure to epidural anesthesia. Of the 20 CpGs in the NHB population showing the strongest mediation effect, 50% demonstrated an average mediation proportion of 52%, with directional consistency of direct and indirect effects. These top 20 CpGs mapped to 21 genes enriched for pathways engaged in antigen processing, antigen presentation, protein ubiquitination and regulatory networks related to the Major Histocompatibility Complex (MHC) class I complex and Nuclear Factor Kappa-B (NFkB) complex. Our findings suggest that DNA methylation in immune-related pathways contributes to the effects of the duration of exposure to epidural anesthesia on childhood asthma risk in NHB offspring.

硬膜外麻醉是一种有效的镇痛方式,广泛应用于分娩镇痛。儿童哮喘是美国最常见的慢性医学疾病之一,对卫生保健系统造成了重大负担。我们最近证明了硬膜外麻醉的持续时间与儿童哮喘的发展之间存在负相关;然而,潜在的分子机制仍不清楚。在这项研究中,来自新生儿表观遗传学研究的127对母婴,包括75对非西班牙裔黑人(NHB)和52对非西班牙裔白人(NHW),我们检验了脐血DNA甲基化介导分娩时硬膜外麻醉暴露时间与儿童哮喘发展之间的关联,以及这种关联是否因种族/民族而异。在NHB血统的母子对中,硬膜外麻醉暴露时间每增加1小时,哮喘风险就会降低(优势比= 0.88,95%可信区间= 0.76-1.01)。NHB人群中中介作用最强的20个CpGs中,有50%的CpGs平均中介比例为52%,直接和间接作用方向一致。这些前20位的CpGs映射到21个基因,这些基因丰富了参与抗原加工、抗原呈递、蛋白质泛素化和与主要组织相容性复合体(MHC) I类复合体和核因子κ b (NFkB)复合体相关的调控网络的途径。我们的研究结果表明,免疫相关途径中的DNA甲基化有助于硬膜外麻醉暴露时间对NHB后代儿童哮喘风险的影响。
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引用次数: 0
COP27 Climate Change Conference: urgent action needed for Africa and the world: Wealthy nations must step up support for Africa and vulnerable countries in addressing past, present and future impacts of climate change. COP27气候变化会议:非洲和世界需要采取紧急行动:富裕国家必须加强对非洲和脆弱国家的支持,以应对气候变化过去、现在和未来的影响。
IF 3.8 Q1 Environmental Science Pub Date : 2022-10-19 eCollection Date: 2022-01-01 DOI: 10.1093/eep/dvac019
Lukoye Atwoli, Gregory E Erhabor, Aiah A Gbakima, Abraham Haileamlak, Jean-Marie Kayembe Ntumba, James Kigera, Laurie Laybourn-Langton, Bob Mash, Joy Muhia, Fhumulani Mavis Mulaudzi, David Ofori-Adjei, Friday Okonofua, Arash Rashidian, Maha El-Adawy, Siaka Sidibé, Abdelmadjid Snouber, James Tumwine, Mohammad Sahar Yassien, Paul Yonga, Lilia Zakhama, Chris Zielinski
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引用次数: 0
European epidemiological patterns of cannabis- and substance-related congenital cardiovascular anomalies: geospatiotemporal and causal inferential study. 欧洲大麻和物质相关先天性心血管异常的流行病学模式:地理时空和因果推理研究。
IF 3.8 Q1 Environmental Science Pub Date : 2022-07-05 eCollection Date: 2022-01-01 DOI: 10.1093/eep/dvac015
Albert Stuart Reece, Gary Kenneth Hulse

As prenatal and community cannabis exposures have recently been linked with congenital heart disease (CHD), it was of interest to explore these associations in Europe in a causal framework and space-time context. Congenital anomaly data from Eurocat, drug-use data from the European Monitoring Centre for Drugs and Drug Addiction, and income from the World Bank. Countries with rising daily cannabis use had in general higher congenital anomaly rates over time than those without (time: status interaction: β-Est. = 0.0267, P = 0.0059). At inverse probability-weighted panel regression, cannabis terms were positive and significant for CHD, severe CHD, atrial septal defect, ventricular septal defect, atrioventricular septal defect, patent ductus arteriosus, tetralogy of Fallot, vascular disruptions, double outlet right ventricle, transposition of the great vessels, hypoplastic right heart, and mitral valve anomalies from 1.75 × 10-19, 4.20 × 10-11, <2.2 × 10-16, <2.2 × 10-16, 1.58 × 10-12, 4.30 × 10-9, 4.36 × 10-16, 3.50 × 10-8, 5.35 × 10-12, <2.2 × 10-16, 5.65 × 10-5 and 6.06 × 10-10. At spatial regression, terms including cannabis were positive and significant for this same list of anomalies from 0.0038, 1.05 × 10-10, 0.0215, 8.94 × 10-6, 1.23 × 10-5, 2.05 × 10-5, 1.07 × 10-6, 8.77 × 10-5, 9.11 × 10-6, 0.0001, 3.10 × 10-7 and 2.17 × 10-7. 92.6% and 75.2% of 149 E-value estimates and minimum E-values were in high zone >9; 100.0% and 98.7% >1.25. Data show many congenital cardiac anomalies exhibit strong bivariate relationships with metrics of cannabis exposure. Causal inferential modelling for the twelve anomalies selected demonstrated convincing evidence of robust relationships to cannabis which survived adjustment and fulfilled epidemiological criteria for causal relationships. Space-time regression was similarly confirmatory. Epigenomic pathways constitute viable potential mechanisms. Given exponential genotoxic dose-response effects, careful and astute control of cannabinoid penetration is indicated.

由于产前和社区大麻暴露最近与先天性心脏病(CHD)有关,因此有兴趣在因果框架和时空背景下探索欧洲的这些关联。先天异常数据来自Eurocat,药物使用数据来自欧洲毒品和毒瘾监测中心,收入数据来自世界银行。随着时间的推移,每天使用大麻的国家的先天性异常率一般高于没有使用大麻的国家(时间:地位相互作用:β-Est = 0.0267, P = 0.0059)。在逆概率加权面板回归中,大麻词汇在冠心病、重度冠心病、房间隔缺损、室间隔缺损、房室间隔缺损、动脉导管未闭、法洛四联症、血管中断、右心室双出口、大血管转位、右心发育不全、二尖瓣异常(1.75 × 10-19、4.20 × 10-11、-16、-16、1.58 × 10-12、4.30 × 10-9、4.36 × 10-16、3.50 × 10-8、5.35 × 10-12)中呈阳性且显著性。-16、5.65 × 10-5和6.06 × 10-10。在空间回归中,包含大麻的术语在0.0038、1.05 × 10-10、0.0215、8.94 × 10-6、1.23 × 10-5、2.05 × 10-5、1.07 × 10-6、8.77 × 10-5、9.11 × 10-6、0.0001、3.10 × 10-7和2.17 × 10-7的异常列表中呈阳性且显著性。149个e值估计值和最小e值的92.6%和75.2%处于>9的高区;100.0%和98.7% >1.25。数据显示,许多先天性心脏异常与大麻暴露指标表现出很强的双变量关系。对所选的12个异常进行因果推理建模,显示了令人信服的证据,证明大麻与调整后的大麻有牢固的关系,并满足了因果关系的流行病学标准。时空回归同样具有证实性。表观基因组途径构成了可行的潜在机制。鉴于指数基因毒性剂量-反应效应,大麻素渗透的谨慎和精明的控制是指。
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引用次数: 8
Effects of cannabis on congenital limb anomalies in 14 European nations: A geospatiotemporal and causal inferential study. 大麻对14个欧洲国家先天性肢体异常的影响:一项地理时空和因果推理研究。
IF 3.8 Q1 Environmental Science Pub Date : 2022-07-05 eCollection Date: 2022-01-01 DOI: 10.1093/eep/dvac016
Albert Stuart Reece, Gary Kenneth Hulse

Cannabinoid exposure is increasing in some European nations. Europe therefore provides an interesting test environment for the recently reported link between cannabis exposure and congenital limb anomaly (CLA) rates (CLARs). Exponential genotoxic dose-response relationships make this investigation both intriguing and imperative. Annual CLAR in 14 nations were from Epidemiological Surveillance of Congenital Anomalies. Drug use rates were from European Monitoring Centre for Drugs and Drug Dependency. Median household income was from the World Bank. E-values provide a quantitative measure of robustness of results to confounding by extraneous covariates. Inverse probability weighting is an important technique for equalizing exposures across countries and removing sources of bias. Rates of CLA, hip dysplasia and the whole group of limb anomalies were higher in countries with increasing daily cannabis use (P = 1.81 × 10-16, 0.0005 and 2.53 × 10-6, respectively). In additive inverse-probability-weighted panel models, the limb reduction-resin Δ9-tetrahydrocannabinol (THC) concentration E-value estimate was 519.93 [95% lower bound (mEV) 49.56], order Resin > Herb ≫ Tobacco > Alcohol. Elevations were noted in 86% E-value estimates and 70.2% of mEVs from 57 E-value pairs from inverse-probability-weighted panel models and from spatial models. As judged by the mEV the degree of association with metrics of cannabis exposure was hip dysplasia > polydactyly > syndactyly > limb anomalies > limb reductions with median E-value estimates from 3.40 × 1065 to 7.06 and median mEVs from 6.14 × 1033 to 3.41. Daily cannabis use interpolated was a more powerful metric of cannabis exposure than herb or resin THC exposure. Data indicate that metrics of cannabis exposure are closely linked with CLAR and satisfy epidemiological criteria for causality. Along with Hawaii and the USA, Europe now forms the third international population in which this causal link has been demonstrated. Cannabis as a predictor of limb anomalies was more potent than tobacco or alcohol. Cannabinoid access should be restricted to protect public health and the community genome/epigenome transgenerationally.

大麻素暴露在一些欧洲国家正在增加。因此,欧洲为最近报道的大麻暴露与先天性肢体异常率(CLARs)之间的联系提供了一个有趣的测试环境。指数型基因毒性剂量-反应关系使这项研究既有趣又势在必行。14个国家的年度CLAR来自先天性异常的流行病学监测。药物使用率来自欧洲药物和药物依赖监测中心。家庭收入中位数来自世界银行。e值提供了对外来协变量混淆的结果稳健性的定量度量。逆概率加权是一种重要的技术,用于平衡各国之间的风险暴露和消除偏差来源。在每日大麻使用量增加的国家,CLA、髋关节发育不良和整组肢体异常的发生率更高(P分别= 1.81 × 10-16、0.0005和2.53 × 10-6)。在加性逆概率加权面板模型中,残肢还原树脂Δ9-tetrahydrocannabinol (THC)浓度e值估计为519.93[95%下限(mEV) 49.56],顺序为树脂>草本>烟草>酒精。从反概率加权面板模型和空间模型的57个e值对中,86%的e值估计和70.2%的mev都注意到了海拔。根据mEV判断,大麻暴露与指标的关联程度为髋关节发育不良>多指畸形>并指畸形>肢体异常>肢体减少,中位e值估计为3.40 × 1065 ~ 7.06,中位mEV为6.14 × 1033 ~ 3.41。每日大麻使用插值是大麻暴露比草药或树脂四氢大麻酚暴露更有力的指标。数据表明,大麻接触指标与CLAR密切相关,并满足因果关系的流行病学标准。与夏威夷和美国一起,欧洲现在形成了第三个证明这种因果关系的国际人口。大麻作为肢体异常的预测因素比烟草或酒精更有效。应限制大麻素的获取,以保护公众健康和跨代社区基因组/表观基因组。
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引用次数: 7
The impact of prenatal and early-life arsenic exposure on epigenetic age acceleration among adults in Northern Chile. 产前和生命早期砷暴露对智利北部成年人表观遗传年龄加速的影响。
IF 3.8 Q1 Environmental Science Pub Date : 2022-06-01 eCollection Date: 2022-01-01 DOI: 10.1093/eep/dvac014
Anne K Bozack, Philippe Boileau, Alan E Hubbard, Fenna C M Sillé, Catterina Ferreccio, Craig M Steinmaus, Martyn T Smith, Andres Cardenas

Exposure to arsenic affects millions of people globally. Changes in the epigenome may be involved in pathways linking arsenic to health or serve as biomarkers of exposure. This study investigated associations between prenatal and early-life arsenic exposure and epigenetic age acceleration (EAA) in adults, a biomarker of morbidity and mortality. DNA methylation was measured in peripheral blood mononuclear cells (PBMCs) and buccal cells from 40 adults (median age = 49 years) in Chile with and without high prenatal and early-life arsenic exposure. EAA was calculated using the Horvath, Hannum, PhenoAge, skin and blood, GrimAge, and DNA methylation telomere length clocks. We evaluated associations between arsenic exposure and EAA using robust linear models. Participants classified as with and without arsenic exposure had a median drinking water arsenic concentration at birth of 555 and 2 μg/l, respectively. In PBMCs, adjusting for sex and smoking, exposure was associated with a 6-year PhenoAge acceleration [B (95% CI)= 6.01 (2.60, 9.42)]. After adjusting for cell-type composition, we found positive associations with Hannum EAA [B (95% CI) = 3.11 (0.13, 6.10)], skin and blood EAA [B (95% CI) = 1.77 (0.51, 3.03)], and extrinsic EAA [B (95% CI) = 4.90 (1.22, 8.57)]. The association with PhenoAge acceleration in buccal cells was positive but not statistically significant [B (95% CI) = 4.88 (-1.60, 11.36)]. Arsenic exposure limited to early-life stages may be associated with biological aging in adulthood. Future research may provide information on how EAA programmed in early life is related to health.

全球数百万人受到砷的影响。表观基因组的变化可能涉及将砷与健康联系起来的途径,或作为暴露的生物标志物。本研究调查了产前和生命早期砷暴露与成人表观遗传年龄加速(EAA)之间的关系,EAA是发病率和死亡率的生物标志物。对40名智利成年人(年龄中位数= 49岁)外周血单核细胞(PBMCs)和颊细胞的DNA甲基化进行了测量,这些成年人在产前和生命早期有或没有高砷暴露。使用Horvath, Hannum, PhenoAge,皮肤和血液,GrimAge和DNA甲基化端粒长度时钟计算EAA。我们使用稳健的线性模型评估砷暴露与EAA之间的关系。被分类为有砷接触和没有砷接触的参与者出生时的饮用水砷浓度中位数分别为555和2 μg/l。在pbmc中,调整性别和吸烟因素后,暴露与6年的表型加速相关[B (95% CI) = 6.01(2.60, 9.42)]。在调整细胞类型组成后,我们发现Hannum EAA [B (95% CI) = 3.11(0.13, 6.10)],皮肤和血液EAA [B (95% CI) = 1.77(0.51, 3.03)]和外源性EAA [B (95% CI) = 4.90(1.22, 8.57)]呈正相关。与颊细胞表型加速呈正相关,但无统计学意义[B (95% CI) = 4.88(-1.60, 11.36)]。仅限于生命早期阶段的砷暴露可能与成年期的生物衰老有关。未来的研究可能会提供早期EAA编程如何与健康相关的信息。
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引用次数: 3
Assessment of parental benzo[a]pyrene exposure-induced cross-generational neurotoxicity and changes in offspring sperm DNA methylome in medaka fish. 评估亲代苯并[a]芘暴露诱导的跨代神经毒性和后代精子DNA甲基化组的变化。
IF 3.8 Q1 Environmental Science Pub Date : 2022-05-27 eCollection Date: 2022-01-01 DOI: 10.1093/eep/dvac013
Teng Wan, Doris Wai-Ting Au, Jiezhang Mo, Lianguo Chen, Kwok-Ming Cheung, Richard Yuen-Chong Kong, Frauke Seemann

Previous studies have revealed that DNA methylation changes could serve as potential genomic markers for environmental benzo[a]pyrene (BaP) exposure and intergenerational inheritance of various physiological impairments (e.g. obesity and reproductive pathologies). As a typical aromatic hydrocarbon pollutant, direct BaP exposure has been shown to induce neurotoxicity. To unravel the inheritance mechanisms of the BaP-induced bone phenotype in freshwater medaka, we conducted whole-genome bisulfite sequencing of F1 sperm and identified 776 differentially methylated genes (DMGs). Ingenuity pathway analysis revealed that DMGs were significantly enriched in pathways associated with neuronal development and function. Therefore, it was hypothesized that parental BaP exposure (1 μg/l, 21 days) causes offspring neurotoxicity. Furthermore, the possibility for sperm methylation as an indicator for a neurotoxic phenotype was investigated. The F0 adult brains and F1 larvae were analyzed for BaP-induced direct and inherited toxicity. Acetylcholinesterase activity was significantly reduced in the larvae, together with decreased swimming velocity. Molecular analysis revealed that the marker genes associated with neuron development and growth (alpha1-tubulin, mbp, syn2a, shh, and gap43) as well as brain development (dlx2, otx2, and krox-20) were universally downregulated in the F1 larvae (3 days post-hatching). While parental BaP exposure at an environmentally relevant concentration could induce neurotoxicity in the developing larvae, the brain function of the exposed F0 adults was unaffected. This indicates that developmental neurotoxicity in larvae may result from impaired neuronal development and differentiation, causing delayed brain growth. The present study demonstrates that the possible adverse health effects of BaP in the environment are more extensive than currently understood. Thus, the possibility of multigenerational BaP toxicity should be included in environmental risk assessments.

先前的研究表明,DNA甲基化变化可以作为环境苯并[a]芘(BaP)暴露和各种生理损伤(如肥胖和生殖疾病)代际遗传的潜在基因组标记。BaP作为一种典型的芳香烃污染物,直接暴露会引起神经毒性。为了揭示淡水medaka中bap诱导的骨表型的遗传机制,我们对F1精子进行了全基因组亚硫酸盐测序,并鉴定了776个差异甲基化基因(dmg)。匠心通路分析显示,dmg显著富集与神经元发育和功能相关的通路。因此,我们假设亲代接触BaP (1 μg/l, 21 d)会导致子代神经毒性。此外,精子甲基化作为神经毒性表型指标的可能性也进行了研究。对F0成虫脑和F1幼虫进行了bap直接毒性和遗传毒性分析。幼虫乙酰胆碱酯酶活性显著降低,游动速度减慢。分子分析显示,与神经元发育和生长相关的标志基因(alpha1-tubulin、mbp、syn2a、shh和gap43)和脑发育相关的标志基因(dlx2、otx2和krox-20)在F1幼虫(孵化后3 d)中普遍下调。虽然与环境相关浓度的亲本BaP暴露会诱发发育中的幼虫的神经毒性,但暴露的F0成虫的脑功能不受影响。这表明幼虫的发育性神经毒性可能是由于神经元发育和分化受损,导致大脑发育迟缓。目前的研究表明,环境中BaP可能对健康造成的不良影响比目前所了解的要广泛得多。因此,多代BaP毒性的可能性应纳入环境风险评估。
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引用次数: 4
Congenital anomaly epidemiological correlates of Δ8THC across USA 2003-16: panel regression and causal inferential study. 2003-16年美国Δ8THC先天性异常流行病学相关性:面板回归和因果推理研究。
IF 3.8 Q1 Environmental Science Pub Date : 2022-05-17 eCollection Date: 2022-01-01 DOI: 10.1093/eep/dvac012
Albert Stuart Reece, Gary Kenneth Hulse

Δ8-Tetrahydrocannabinol (Δ8THC) is marketed in many US states as 'legal weed'. Concerns exist relating to class-wide genotoxic cannabinoid effects. We conducted an epidemiological investigation of Δ8THC-related genotoxicity expressed as 57 congenital anomaly (CA) rates (CARs) in the USA. CARs were taken from the Centers for Disease Control, Atlanta, Georgia. Drug exposure data were taken from the National Survey of Drug Use and Health, with a response rate of 74.1%. Ethnicity and income data were taken from the US Census Bureau. National cannabinoid exposure was taken from Drug Enforcement Agency publications and multiplied by state cannabis use data to derive state-based estimates of Δ8THC exposure. At bivariate continuous analysis, Δ8THC was associated with 23 CAs on raw CA rates, 33 CARs after correction for early termination for anomaly estimates and 41 on a categorical analysis comparing the highest and lowest exposure quintiles. At inverse probability weighted multivariable additive and interactive models lagged to 0, 2 and 4 years, Δ8THC was linked with 39, 8, 4 and 9 CAs. Chromosomal, cardiovascular, gastrointestinal, genitourinary, limb, central nervous system (CNS) and face systems were particularly affected. The minimum E-values ranged to infinity. Both the number of anomalies implicated and the effect sizes demonstrated were much greater for Δ8THC than for tobacco and alcohol combined. Δ8THC appears epidemiologically to be more strongly associated with many CAs than for tobacco and alcohol and is consistent with a cannabinoid class genotoxic/epigenotoxic effect. Quantitative causality criteria were fulfilled, and causal relationships either for Δ8THC or for cannabinoid/s, for which it is a surrogate marker, may be in operation.

Δ8-Tetrahydrocannabinol (Δ8THC)在美国许多州作为“合法大麻”销售。存在与类全遗传毒性大麻素效应有关的担忧。我们在美国进行了一项以57例先天性异常(CA)率(CARs)表达的Δ8THC-related遗传毒性的流行病学调查。汽车是从乔治亚州亚特兰大的疾病控制中心拿走的。药物暴露数据来源于全国药物使用与健康调查,回复率为74.1%。种族和收入数据来自美国人口普查局。全国大麻素暴露量取自缉毒局出版物,并乘以各州大麻使用数据,得出各州对Δ8THC暴露量的估计。在双变量连续分析中,Δ8THC与23例原始CA发生率相关,33例早期终止异常估计校正后的CA, 41例比较最高和最低暴露五分位数的分类分析相关。在负概率加权多变量相加和交互模型滞后于0、2和4年,Δ8THC与39、8、4和9个ca相关。染色体、心血管、胃肠道、泌尿生殖系统、肢体、中枢神经系统(CNS)和面部系统受到特别影响。最小e值的范围为无穷大。与烟草和酒精的总和相比,Δ8THC所涉及的异常数量和所显示的效应量都要大得多。Δ8THC在流行病学上似乎与许多ca的相关性比与烟草和酒精的相关性更强,并且与大麻素类遗传毒性/表观遗传毒性作用一致。定量因果关系标准得到满足,Δ8THC或作为替代标记物的大麻素/s的因果关系可能在起作用。
{"title":"Congenital anomaly epidemiological correlates of Δ8THC across USA 2003-16: panel regression and causal inferential study.","authors":"Albert Stuart Reece,&nbsp;Gary Kenneth Hulse","doi":"10.1093/eep/dvac012","DOIUrl":"https://doi.org/10.1093/eep/dvac012","url":null,"abstract":"<p><p>Δ8-Tetrahydrocannabinol (Δ8THC) is marketed in many US states as 'legal weed'. Concerns exist relating to class-wide genotoxic cannabinoid effects. We conducted an epidemiological investigation of Δ8THC-related genotoxicity expressed as 57 congenital anomaly (CA) rates (CARs) in the USA. CARs were taken from the Centers for Disease Control, Atlanta, Georgia. Drug exposure data were taken from the National Survey of Drug Use and Health, with a response rate of 74.1%. Ethnicity and income data were taken from the US Census Bureau. National cannabinoid exposure was taken from Drug Enforcement Agency publications and multiplied by state cannabis use data to derive state-based estimates of Δ8THC exposure. At bivariate continuous analysis, Δ8THC was associated with 23 CAs on raw CA rates, 33 CARs after correction for early termination for anomaly estimates and 41 on a categorical analysis comparing the highest and lowest exposure quintiles. At inverse probability weighted multivariable additive and interactive models lagged to 0, 2 and 4 years, Δ8THC was linked with 39, 8, 4 and 9 CAs. Chromosomal, cardiovascular, gastrointestinal, genitourinary, limb, central nervous system (CNS) and face systems were particularly affected. The minimum <i>E</i>-values ranged to infinity. Both the number of anomalies implicated and the effect sizes demonstrated were much greater for Δ8THC than for tobacco and alcohol combined. Δ8THC appears epidemiologically to be more strongly associated with many CAs than for tobacco and alcohol and is consistent with a cannabinoid class genotoxic/epigenotoxic effect. Quantitative causality criteria were fulfilled, and causal relationships either for Δ8THC or for cannabinoid/s, for which it is a surrogate marker, may be in operation.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2022-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/5e/00/dvac012.PMC9245652.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40466413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 8
Nephrotoxicity of perfluorooctane sulfonate (PFOS)-effect on transcription and epigenetic factors. 全氟辛烷磺酸(PFOS)的肾毒性——对转录和表观遗传因子的影响
IF 4.8 Q1 GENETICS & HEREDITY Pub Date : 2022-04-16 eCollection Date: 2022-01-01 DOI: 10.1093/eep/dvac010
Yi Wen, Faizan Rashid, Zeeshan Fazal, Ratnakar Singh, Michael J Spinella, Joseph Irudayaraj

Perfluorooctane sulfonate (PFOS) is a widespread persistent environmental pollutant implicated in nephrotoxicity with altered metabolism, carcinogenesis, and fibrosis potential. We studied the underlying epigenetic mechanism involving transcription factors of PFOS-induced kidney injury. A 14-day orally dosed mouse model was chosen to study acute influences in vivo. Messenger RNA expression analysis and gene set enrichment analysis were performed to elucidate the relationship between epigenetic regulators, transcription factors, kidney disease, and metabolism homeostasis. PFOS was found to accumulate in mouse kidney in a dose-dependent manner. Kidney injury markers Acta2 and Bcl2l1 increased in expression significantly. Transcription factors, including Nef2l2, Hes1, Ppara, and Ppard, were upregulated, while Smarca2 and Pparg were downregulated. Furthermore, global DNA methylation levels decreased and the gene expression of histone demethylases Kdm1a and Kdm4c were upregulated. Our work implicates PFOS-induced gene expression alterations in epigenetics, transcription factors, and kidney biomarkers with potential implications for kidney fibrosis and kidney carcinogenesis. Future experiments can focus on epigenetic mechanisms to establish a panel of PFOS-induced biomarkers for nephrotoxicity evaluation.

摘要全氟辛烷磺酸(PFOS)是一种广泛存在的持久性环境污染物,与肾毒性有关,具有改变代谢、致癌和纤维化的潜力。我们研究了涉及全氟辛烷磺酸诱导的肾损伤的转录因子的潜在表观遗传学机制。选择14天口服给药的小鼠模型来研究体内的急性影响。信使核糖核酸表达分析和基因集富集分析旨在阐明表观遗传学调节因子、转录因子、肾脏疾病和代谢稳态之间的关系。发现全氟辛烷磺酸以剂量依赖的方式在小鼠肾脏中积累。肾损伤标志物Acta2和Bcl2l1的表达显著增加。转录因子,包括Nef2l2、Hes1、Ppara和Ppard,上调,而Smarca2和Pparg下调。此外,整体DNA甲基化水平降低,组蛋白去甲基化酶Kdm1a和Kdm4c的基因表达上调。我们的研究表明,全氟辛烷磺酸诱导的表观遗传学、转录因子和肾脏生物标志物的基因表达改变可能与肾脏纤维化和肾脏癌变有关。未来的实验可以侧重于表观遗传学机制,以建立一组全氟辛烷磺酸诱导的肾毒性评估生物标志物。
{"title":"Nephrotoxicity of perfluorooctane sulfonate (PFOS)-effect on transcription and epigenetic factors.","authors":"Yi Wen, Faizan Rashid, Zeeshan Fazal, Ratnakar Singh, Michael J Spinella, Joseph Irudayaraj","doi":"10.1093/eep/dvac010","DOIUrl":"10.1093/eep/dvac010","url":null,"abstract":"<p><p>Perfluorooctane sulfonate (PFOS) is a widespread persistent environmental pollutant implicated in nephrotoxicity with altered metabolism, carcinogenesis, and fibrosis potential. We studied the underlying epigenetic mechanism involving transcription factors of PFOS-induced kidney injury. A 14-day orally dosed mouse model was chosen to study acute influences <i>in vivo</i>. Messenger RNA expression analysis and gene set enrichment analysis were performed to elucidate the relationship between epigenetic regulators, transcription factors, kidney disease, and metabolism homeostasis. PFOS was found to accumulate in mouse kidney in a dose-dependent manner. Kidney injury markers <i>Acta2</i> and <i>Bcl2l1</i> increased in expression significantly. Transcription factors, including <i>Nef2l2, Hes1, Ppara</i>, and <i>Ppard,</i> were upregulated, while <i>Smarca2</i> and <i>Pparg</i> were downregulated. Furthermore, global DNA methylation levels decreased and the gene expression of histone demethylases <i>Kdm1a</i> and <i>Kdm4c</i> were upregulated. Our work implicates PFOS-induced gene expression alterations in epigenetics, transcription factors, and kidney biomarkers with potential implications for kidney fibrosis and kidney carcinogenesis. Future experiments can focus on epigenetic mechanisms to establish a panel of PFOS-induced biomarkers for nephrotoxicity evaluation.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2022-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9134076/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45927022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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Environmental Epigenetics
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