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- Gliga, Anda R, et al.
(författare)
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Prenatal arsenic exposure is associated with increased plasma IGFBP3 concentrations in 9-year-old children partly via changes in DNA methylation
- 2018
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Ingår i: Archives of Toxicology. - : Springer Science and Business Media LLC. - 0340-5761 .- 1432-0738. ; 92:8, s. 2487-2500
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Tidskriftsartikel (refereegranskat)abstract
- Exposure to inorganic arsenic (As), a carcinogen and epigenetic toxicant, has been associated with lower circulating levels of insulin-like growth factor 1 (IGF1) and impaired growth in children of pre-school age. The aim of this study was to assess the potential impact of exposure to As on IGF1 and insulin-like growth factor-binding protein 3 (IGFBP3) as well as DNA methylation changes in 9-year-old children. To this end, we studied 9-year-old children from a longitudinal mother-child cohort in rural Bangladesh (n = 551). Prenatal and concurrent exposure to As was assessed via concentrations in maternal urine at gestational week 8 and in child urine at 9 years, measured by HPLC-HG-ICPMS. Plasma IGF1 and IGFBP3 concentrations were quantified with immunoassays. DNA methylation was measured in blood mononuclear cells at 9 years in a sub-sample (n = 113) using the Infinium HumanMethylation450K BeadChip. In multivariable-adjusted linear regression models, prenatal As (natural log-transformed), but not children's concurrent urinary As, was positively associated with IGFBP3 concentrations (β = 76, 95% CI 19, 133). As concentrations were not associated with IGF1. DNA methylation analysis revealed CpGs associated with both prenatal As and IGFBP3. Mediation analysis suggested that methylation of 12 CpG sites for all children was mediator of effect for the association between prenatal As and IGFBP3. We also found differentially methylated regions, generally hypermethylated, that were associated with both prenatal As and IGFBP3. In all, our study revealed that prenatal exposure to As was positively associated with IGFBP3 concentrations in children at 9 years, independent of IGF1, and this association may, at least in part, be epigenetically mediated.
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| 2. |
- Skröder, Helena, et al.
(författare)
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Associations between methylated metabolites of arsenic and selenium in urine of pregnant bangladeshi women and interactions between the main genes involved
- 2018
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Ingår i: Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 126:2
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: It has been proposed that interactions between selenium and arsenic in the body may affect their kinetics and toxicity. However, it is unknown how the elements influence each other in humans. OBJECTIVES: We aimed to investigate potential interactions in the methylation of selenium and arsenic. METHODS: Urinary selenium (U-Se) and arsenic (U-As) were measured using inductively coupled plasma mass spectrometry (ICPMS) in samples collected from pregnant women (n = 226) in rural Bangladesh at gestational weeks (GW) 8, 14, 19, and 30. Urinary concentrations of trimethyl seleno-nium ion (TMSe) were measured by HPLC–vapor generation–ICPMS, as were inorganic arsenic (iAs), methylarsonic acid (MMA), and dimethylarsinic acid (DMA). Methylation efficiency was assessed based on relative amounts (%) of arsenic and selenium metabolites in urine. Genotyping for the main arsenite and selenium methyltransferases, AS3MT and INMT, was performed using TaqMan probes or Sequenom. RESULTS: Multivariable-adjusted linear regression analyses indicated that %TMSe (at GW8) was positively associated with %MMA (β =1.3, 95% CI: 0.56, 2.0) and U-As, and inversely associated with %DMA and U-Se in producers of TMSe (INMT rs6970396 AG + AA, n = 74), who had a wide range of urinary TMSe (12–42%). Also, %TMSe decreased in parallel to %MMA during pregnancy, especially in the first trimester (−0.58 %TMSe per gestational week). We found a gene–gene interaction for %MMA (p-interaction = 0.076 for haplotype 1). In analysis stratified by INMT genotype, the association between %MMA and both AS3MT haplotypes 1 and 3 was stronger in women with the INMT GG (TMSe nonproducers, 5th–95th percentile: 0.2–2%TMSe) vs. AG + AA genotype. CONCLUSIONS: Our findings for Bangladeshi women suggest a positive association between urinary %MMA and %TMSe. Genes involved in the methylation of selenium and arsenic may interact on associations with urinary %MMA.
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| 3. |
- Skröder Löveborn, Helena
(författare)
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Early-life selenium status and cognitive development
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Selenium is an essential element that is found in food sources such as meat, fish, and cereals. The essentiality of selenium was demonstrated in the 1950s, and the interest in its health effects has been growing ever since. Deficiency is common world-wide, particularly in Europe and south-eastern Asia. It has been estimated that 0.5-1 billion people could be selenium deficient. Previous studies regarding health effects of selenium have focused on the impact of deficiency for the risk of cancer, cardiovascular disease, and decreased fertility and immune function. Lately, the importance for brain function has also become the focus of many studies assessing potential protection against cognitive decline and certain neurodegenerative diseases, such as Alzheimer’s and Parkinson’s disease. However, little is known about the importance for early-life development. In particular, the role of selenium in cognitive development has not been studied, even though the brain is one of the organs with highest selenium priority at deficient intake levels. Therefore, the overall aim of this thesis was to assess whether selenium status in early life is important for cognitive development. The studies included in this thesis were based on data from a large mother-child cohort in rural Bangladesh. The cohort was nested in a randomized food and micronutrient supplementation trial that was established in 2001-2003, called the Maternal and Infant Nutrition Intervention, Matlab (MINIMat). Women were recruited to this nested cohort early in pregnancy (at pregnancy testing), and donated urine and blood samples continuously throughout pregnancy. The subsequently born children were divided into two groups for different outcome assessments. For cognitive assessment, children were followed-up at 1.5, 5, and 10 years, while assessment of immune function and various effect biomarkers was performed in the other group of children at 4.5 and 9 years of age. To evaluate the role of selenium in cognitive development, concentrations of the element were measured in urine and blood from the pregnant women, and also in blood, urine, and hair from the Bangladeshi children at different ages (n=223-1408). Results from the group of children who donated blood, urine, and hair, demonstrated that also hair selenium could be used for assessment of selenium status in the present population. Using multivariable-adjusted regression analyses, we found that adequate selenium status during pregnancy seemed important for the children’s cognitive development. Children born to mothers with higher selenium status performed better on the cognitive tests at 1.5, 5 and 10 years of age. Also the selenium status during early childhood seemed to be important for the cognitive abilities at the 5- and 10-year follow-ups. There was an indication of an upper limit for the positive association, in line with the narrow therapeutic interval for selenium. Assessment of influential factors for the selenium biomarkers indicated that exposure to arsenic and cadmium (both strong pro-oxidants) changed the distribution of selenium between different biological compartments (or vice versa). Importantly, malnourished children seemed to retain more selenium, supporting that the regulation of selenium occurs through changes in urinary excretion also in children. To conclude, this research, based on different biomarkers of selenium status and comprehensive testing of cognitive abilities in large samples of children at 1.5 (n=729), 5 (n=1260) and 10 (n=1408) years of age provides substantial, new evidence of the importance of adequate early-life selenium status for brain development. Similar studies in other populations, as well as research on efficient ways to improve inadequate selenium status without risking selenium toxicity, are warranted.
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