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Imprinted genes and the environment: links to the toxic metals arsenic, cadmium, lead and mercury.

ABSTRACT: Imprinted genes defy rules of Mendelian genetics with their expression tied to the parent from whom each allele was inherited. They are known to play a role in various diseases/disorders including fetal growth disruption, lower birth weight, obesity, and cancer. There is increasing interest in understanding their influence on environmentally-induced disease. The environment can be thought of broadly as including chemicals present in air, water and soil, as well as food. According to the Agency for Toxic Substances and Disease Registry (ATSDR), some of the highest ranking environmental chemicals of concern include metals/metalloids such as arsenic, cadmium, lead and mercury. The complex relationships between toxic metal exposure, imprinted gene regulation/expression and health outcomes are understudied. Herein we examine trends in imprinted gene biology, including an assessment of the imprinted genes and their known functional roles in the cell, particularly as they relate to toxic metals exposure and disease. The data highlight that many of the imprinted genes have known associations to developmental diseases and are enriched for their role in the TP53 and AhR pathways. Assessment of the promoter regions of the imprinted genes resulted in the identification of an enrichment of binding sites for two transcription factor families, namely the zinc finger family II and PLAG transcription factors. Taken together these data contribute insight into the complex relationships between toxic metals in the environment and imprinted gene biology.

SUBMITTER: Smeester L

PROVIDER: S-EPMC4094944 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundStudies have found that toxic heavy metals exposure could induce the generation of reactive oxygen species (ROS), and is of epigenetic effect, which might be associated with the occurrence of Autistic Disorder (ASD). This systematic review and meta-analysis aims to elucidate the association between exposure to 4 heavy metals, cadmium (Cd), lead (Pb), arsenic(As), and mercury (Hg), and the occurrence of ASD in children.MethodsWe searched PubMed, Web of Science, Embase, and Cochrane Library, from their inception to October 2022, for epidemiological investigations that explore the association between exposure to Cd, Pb, As, or Hg and the occurrence of child ASD.ResultsA total of 53 studies were included, involving 5,054 individuals aged less than 18 (2,533 ASD patients and 2,521 healthy controls). Compared with the healthy controls, in hair and blood tests, concentrations of the 4 heavy metals were significantly higher in the ASD group than in the healthy control group, and the differences in Pb, arsenic and Hg were statistically significant (P < 0.05). In the urine test, concentrations of arsenic and Hg were significantly higher in the ASD group than in the healthy control group (P < 0.05), while the results of Cd and Pb were opposite to those of arsenic and Hg (P > 0.05). Subgroup analysis for geographic regions showed that ASD patients in Asia and Europe had higher concentrations of the 4 heavy metals, compared with the healthy controls, in which the differences in Pb, arsenic, and Hg were statistically significant (P < 0.05), while in North America, the healthy controls had higher Cd, arsenic, and Hg concentrations (P > 0.05).ConclusionCompared with the healthy control group, the ASD group had higher concentrations of Cd, Pb, arsenic, and Hg. These 4 heavy metals play different roles in the occurrence and progression of ASD. Moreover, there is significant heterogeneity among the included studies due to controversies about the study results among different countries and regions and different sources of detection materials. The results of this study firmly support the policies to limit heavy metals exposure, especially among pregnant women and young children, so as to help reduce the incidence of ASD.

Project description:BACKGROUND:Occupational and environmental exposures to toxic metals are established risk factors for the development of hypertension and kidney disease in adults. There is some evidence of developmental metal nephrotoxicity in children and from animal studies; however, to our knowledge no previous studies have examined associations between co-exposure to nephrotoxic environmental metals and children's kidney health. OBJECTIVE:The objective of this study was to assess the association between co-exposure to lead (Pb), cadmium (Cd), mercury (Hg), and arsenic (As), measured in urine and blood, and kidney parameters in US adolescents. METHODS:We performed a cross-sectional analysis of a subsample of 2709 children aged 12-19 participating in the National Health and Nutrition Examination Survey (NHANES) between 2009 and 2014. We analyzed urine levels of 4 nephrotoxic metals selected a priori (As, Cd, Pb and Hg), Umix, and 3 nephrotoxic metals in blood (Cd, Pb, and Hg), Bmix, using a weighted quantile sum (WQS) approach. We applied WQS regression to analyze the association of Bmix and Umix with estimated glomerular filtration rate (eGFR), serum uric acid (SUA), urine albumin, blood urea nitrogen (BUN), and systolic blood pressure (SBP), adjusting for sex, race/ethnicity, age, head of household's education level, height, BMI, serum cotinine, and NHANES cohort year. Umix and urine albumin models were also adjusted for urine creatinine, and Bmix models were also adjusted for fish consumption. Subanalyses included stratification by sex and an arsenic-only model including six speciated forms of As measured in urine. RESULTS:In WQS regression models, each decile increase of Umix was associated with 1.6% (95% CI: 0.5, 2.8) higher BUN, 1.4% (95% CI: 0.7, 2.0) higher eGFR, and 7.6% (95% CI: 2.4, 13.1) higher urine albumin. The association between Umix and BUN was primarily driven by As (72%), while the association with eGFR was driven by Hg (61%), and Cd (17%), and the association with urine albumin was driven by Cd (37%), Hg (33%), and Pb (25%). There was no significant relationship between Umix and SUA or SBP. In WQS models using the combined blood metals, Bmix, each decile increase of Bmix was associated with 0.6% (95% CI: 0.0, 1.3) higher SUA; this association was driven by Pb (43%), Hg (33%), and Cd (24%) and was marginally significant (p?=?0.05). No associations were observed between Bmix and urine albumin, eGFR, BUN, or SBP. CONCLUSIONS:The findings suggest metals including As, Pb, Hg, Cd and their combinations may affect renal parameters, although potential reverse causation cannot be ruled out due to the cross-sectional study design. Implications of early life low-level exposure to multiple metals on kidney function may have far-reaching consequences later in life in the development of hypertension, kidney disease, and renal dysfunction. Longitudinal studies should further evaluate these relationships.

Project description:BackgroundWe have recently shown that biomarker levels of selected metals are higher in Asians than in other U.S. ethnic groups, with important differences within selected Asian subgroups. Much of this difference may be dietary in origin; however, this is not well established.ObjectiveWe evaluated dietary intake of toxic metals as a source of increased biomarker levels of metals among U.S. Asians.MethodsWe estimated daily food consumption and dietary intake of arsenic, cadmium, lead, and mercury by combining 24-hr dietary intake recall data from the 2011-2012 National Health and Nutrition Examination Survey (NHANES) with data from the USDA Food Composition Intake Database and FDA Total Dietary Study. We analyzed associations between dietary metal intake and biomarker levels of the metals using linear regression. Further, estimated food consumption and metal intake levels were compared between Asians and other racial/ethnic groups (white, black, Mexican American, and other Hispanic) and within three Asian subgroups (Chinese, Indian Asian, and other Asians).ResultsSignificant associations (p < 0.05) were found between biomarker levels and estimated dietary metal intake for total and inorganic arsenic and mercury among Asians. Asians had the highest daily fish and rice consumption across the racial/ethnic groups. Fish was the major contributor to dietary mercury and total arsenic intake, whereas rice was the major contributor to inorganic arsenic dietary intake. Fish consumption across the Asian subgroups varied, with Asian Indians having lower fish consumption than the other Asian subgroups. Rice consumption was similar across the Asian subgroups.ConclusionsWe confirmed that estimated dietary intake of arsenic (total and inorganic) and mercury is significantly associated with their corresponding biomarkers in U.S. Asians, using nationally representative data. In contrast, estimated dietary intake of cadmium and lead were not significantly associated with their corresponding biomarker levels in U.S. Asians. Citation: Awata H, Linder S, Mitchell LE, Delclos GL. 2017. Association of dietary intake and biomarker levels of arsenic, cadmium, lead, and mercury among Asian populations in the United States: NHANES 2011-2012. Environ Health Perspect 125:314-323;?http://dx.doi.org/10.1289/EHP28.

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Imprinted genes and the environment: links to the toxic metals arsenic, cadmium, lead and mercury.

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