| 1. |
- Lozano, Manuel, et al.
(författare)
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DNA methylation changes associated with prenatal mercury exposure : A meta-analysis of prospective cohort studies from PACE consortium
- 2022
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Ingår i: Environmental Research. - : Elsevier BV. - 0013-9351 .- 1096-0953. ; 204
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Tidskriftsartikel (refereegranskat)abstract
- Mercury (Hg) is a ubiquitous heavy metal that originates from both natural and anthropogenic sources and is transformed in the environment to its most toxicant form, methylmercury (MeHg). Recent studies suggest that MeHg exposure can alter epigenetic modifications during embryogenesis. In this study, we examined associations between prenatal MeHg exposure and levels of cord blood DNA methylation (DNAm) by meta-analysis in up to seven independent studies (n = 1462) as well as persistence of those relationships in blood from 7 to 8 year-old children (n = 794). In cord blood, we found limited evidence of differential DNAm at cg24184221 in MED31 (β = 2.28 × 10−4, p-value = 5.87 × 10−5) in relation to prenatal MeHg exposure. In child blood, we identified differential DNAm at cg15288800 (β = 0.004, p-value = 4.97 × 10−5), also located in MED31. This repeated link to MED31, a gene involved in lipid metabolism and RNA Polymerase II transcription function, may suggest a DNAm perturbation related to MeHg exposure that persists into early childhood. Further, we found evidence for association between prenatal MeHg exposure and child blood DNAm levels at two additional CpGs: cg12204245 (β = 0.002, p-value = 4.81 × 10−7) in GRK1 and cg02212000 (β = −0.001, p-value = 8.13 × 10−7) in GGH. Prenatal MeHg exposure was associated with DNAm modifications that may influence health outcomes, such as cognitive or anthropometric development, in different populations.
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| 2. |
- Lozano, Manuel, et al.
(författare)
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Prenatal Metals Exposure and pre-adolescents’ Emotional and Behavioral Problems
- 2023
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Ingår i: Exposure and Health. - 2451-9766.
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Tidskriftsartikel (refereegranskat)abstract
- Emotional and behavioral problems during childhood raise the risk of subsequent developmental of mental disorders. Our aim was to study the association between maternal metal and trace element concentrations during gestation and these problems in 9 year-old children. The study sample comprised Spanish mother-child pairs in the INMA project (n = 1003). Metals and trace elements (As, Cd, Co, Cu, Mo, Ni, Pb, Sb, Se, Tl and Zn) were measured in urine samples collected during pregnancy. Inorganic As metabolites were speciated in a subsample (n = 729). Emotional and behavioral problems were assessed using the Child Behavior Checklist (CBCL) composed of three scales: internalizing, externalizing and total problems. Sociodemographic, dietary and exposure to other environmental pollutants were obtained through questionnaires. Single nucleotide polymorphisms in brain- and metabolism-related genes APOE, BDNF, GSTP1, and PON1 were determined in cord blood. Multivariate negative binomial models were used. The interaction with sex and genotypes was evaluated including interaction terms. A multi-element analysis was carried out by a principal component analysis. Higher concentrations of Cu, monomethylarsonic acid, and Pb during pregnancy were associated with an increased incidence ratio risk (IRR) between 4.6 and 7.5% for internalizing and externalizing problems for all three CBCL scales in the children. Increasing Mo, Ni and Co concentrations were associated with higher IRR for internalizing problems (up to 8%), and Cd for externalizing problems (6.7%). Modifications by sex and genotypes were found for several associations. Multi-element analysis associated multiple metals and trace elements (Ni, Cu, Se, Cd and Pb) with higher internalizing problems.
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| 3. |
- Soler-Blasco, Raquel, et al.
(författare)
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Genetic Susceptibility to Neurotoxicity Related to Prenatal Inorganic Arsenic Exposure in Young Spanish Children.
- 2023
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Ingår i: Environmental science & technology. - 1520-5851. ; 57:41, s. 15366-15378
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Tidskriftsartikel (refereegranskat)abstract
- We explored the influence of child and maternal single nucleotide polymorphisms (SNPs) in genes related to neurological function and arsenic metabolism (i.e., ABCA1, ABCB1, PON1, CYP3A, BDNF, GSTP1, MT2A, and APOE as well as AS3MT) on the association between prenatal arsenic (As) exposure and methylation efficiency and neuropsychological development in 4-5-year-old children. Participants were 549 mother-child pairs from the INMA (Environment and Childhood) Spanish Project. We measured inorganic arsenic (iAs) and the metabolites monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) in urine samples collected during pregnancy. Neuropsychological development was assessed at the age of 4-5 years using the McCarthy Scales of Children's Abilities (MSCA). Several SNPs were determined in maternal and child DNA; AS3MT and APOE haplotypes were inferred. The median ∑As (sum of iAs, DMA, and MMA) was 7.08 μg/g creatinine. Statistically significant interactions for children's APOE haplotype were observed. Specifically, ε4-carrier children had consistently lower MSCA scores in several scales with increasing ∑As and MMA concentrations. These results provide evidence regarding the neurotoxic effects of early life exposure to As, observing that the APOE ε4 allele could make children more vulnerable to this exposure.
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