| 1. |
- Chatziioannou, Aristotelis, et al.
(författare)
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Blood-based omic profiling supports female susceptibility to tobacco smoke-induced cardiovascular diseases
- 2017
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- We recently reported that differential gene expression and DNA methylation profiles in blood leukocytes of apparently healthy smokers predicts with remarkable efficiency diseases and conditions known to be causally associated with smoking, suggesting that blood-based omic profiling of human populations may be useful for linking environmental exposures to potential health effects. Here we report on the sex-specific effects of tobacco smoking on transcriptomic and epigenetic features derived from genome-wide profiling in white blood cells, identifying 26 expression probes and 92 CpG sites, almost all of which are affected only in female smokers. Strikingly, these features relate to numerous genes with a key role in the pathogenesis of cardiovascular disease, especially thrombin signaling, including the thrombin receptors on platelets F2R (coagulation factor II (thrombin) receptor; PAR1) and GP5 (glycoprotein 5), as well as HMOX1 (haem oxygenase 1) and BCL2L1 (BCL2-like 1) which are involved in protection against oxidative stress and apoptosis, respectively. These results are in concordance with epidemiological evidence of higher female susceptibility to tobacco-induced cardiovascular disease and underline the potential of blood-based omic profiling in hazard and risk assessment.
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| 2. |
- Rignell-Hydbom, Anna, et al.
(författare)
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Exposure to p,p'-DDE: a risk factor for type 2 diabetes.
- 2009
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 4:10
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Persistent organic pollutants (POPs), such as PCBs, DDT and dioxins have in several cross-sectional studies shown strong associations with type 2 diabetes mellitus. Reversed causality can however not be excluded. The aim of this case-control study was to evaluate whether POPs concentration is a risk factor for type 2 diabetes. METHODOLOGY/PRINCIPAL FINDINGS: A case-control study was performed within a well-defined cohort of women, age 50-59 years, from the Southern part of Sweden. Biomarkers for POP exposure, 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p'-DDE) were analyzed in stored serum samples, which were collected at the baseline examination when the cohort was established. For 107 out of the 371 cases, serum samples were stored at least three years before their type 2 diabetes was diagnosed. In this data set, CB-153 and p,p'-DDE were not associated with an increased risk to develop type 2 diabetes. However, when only the cases (n = 39) that were diagnosed more than six years after the baseline examination and their controls were studied, the women in the highest exposed quartile showed an increased risk to develop type 2 diabetes (OR of 1.6 [95% 0.61, 4.0] for CB-153 and 5.5 [95% CI 1.2, 25] for p,p'-DDE). CONCLUSIONS/SIGNIFICANCE: The results from the present case-control study, including a follow-up design, confirms that p,p'-DDE exposure can be a risk factor for type 2 diabetes.
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| 3. |
- Schillemans, Tessa, et al.
(författare)
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Plasma metabolites associated with exposure to perfluoroalkyl substances and risk of type 2 diabetes – A nested case-control study
- 2021
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Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 146
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Tidskriftsartikel (refereegranskat)abstract
- Perfluoroalkyl substances (PFAS) are widespread persistent environmental pollutants. There is evidence that PFAS induce metabolic perturbations in humans, but underlying mechanisms are still unknown. In this exploratory study, we investigated PFAS-related plasma metabolites for their associations with type 2 diabetes (T2D) to gain potential mechanistic insight in these perturbations. We used untargeted LC-MS metabolomics to find metabolites related to PFAS exposures in a case-control study on T2D (n = 187 matched pairs) nested within the Västerbotten Intervention Programme cohort. Following principal component analysis (PCA), six PFAS measured in plasma appeared in two groups: 1) perfluorononanoic acid, perfluorodecanoic acid and perfluoroundecanoic acid and 2) perfluorohexane sulfonic acid, perfluorooctane sulfonic acid and perfluorooctanoic acid. Using a random forest algorithm, we discovered metabolite features associated with individual PFAS and PFAS exposure groups which were subsequently investigated for associations with risk of T2D. PFAS levels correlated with 171 metabolite features (0.16 ≤ |r| ≤ 0.37, false discovery rate (FDR) adjusted p < 0.05). Out of these, 35 associated with T2D (p < 0.05), with 7 remaining after multiple testing adjustment (FDR < 0.05). PCA of the 35 PFAS- and T2D-related metabolite features revealed two patterns, dominated by glycerophospholipids and diacylglycerols, with opposite T2D associations. The glycerophospholipids correlated positively with PFAS and associated inversely with risk for T2D (Odds Ratio (OR) per 1 standard deviation (1-SD) increase in metabolite PCA pattern score = 0.2; 95% Confidence Interval (CI) = 0.1–0.4). The diacylglycerols also correlated positively with PFAS, but they associated with increased risk for T2D (OR per 1-SD = 1.9; 95% CI = 1.3–2.7). These results suggest that PFAS associate with two groups of lipid species with opposite relations to T2D risk.
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| 4. |
- Gennings, Chris, et al.
(författare)
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Incorporating regulatory guideline values in analysis of epidemiology data
- 2018
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Ingår i: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 120, s. 535-543
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Tidskriftsartikel (refereegranskat)abstract
- Fundamental to regulatory guidelines is to identify chemicals that are implicated with adverse human health effects and inform public health risk assessors about “acceptable ranges” of such environmental exposures (e.g., from consumer products and pesticides). The process is made more difficult when accounting for complex human exposures to multiple environmental chemicals. Herein we propose a new class of nonlinear statistical models for human data that incorporate and evaluate regulatory guideline values into analyses of health effects of exposure to chemical mixtures using so-called ‘desirability functions’ (DFs). The DFs are incorporated into nonlinear regression models to allow for the simultaneous estimation of points of departure for risk assessment of combinations of individual substances that are parts of chemical mixtures detected in humans. These are, in contrast to published so-called biomonitoring equivalent (BE) values and human biomonitoring (HBM) values that link regulatory guideline values from in vivo studies of single chemicals to internal concentrations monitored in humans. We illustrate the strategy through the analysis of prenatal concentrations of mixtures of 11 chemicals with suspected endocrine disrupting properties and two health effects: birth weight and language delay at 2.5 years. The strategy allows for the creation of a Mixture Desirability Function i.e., MDF, which is a uni-dimensional construct of the set of single chemical DFs; thus, it focuses the resulting inference to a single dimension for a more powerful one degree-of-freedom test of significance. Based on the application of this new method we conclude that the guideline values need to be lower than those for single chemicals when the chemicals are observed in combination to achieve a similar level of protection as was aimed for the individual chemicals. The proposed modeling may thus suggest data-driven uncertainty factors for single chemical risk assessment that takes environmental mixtures into account.
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| 5. |
- Krauskopf, Julian, et al.
(författare)
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MicroRNA profile for health risk assessment : environmental exposure to persistent organic pollutants strongly affects the human blood microRNA machinery
- 2017
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Persistent organic pollutants (POPs) are synthetic chemical substances that accumulate in our environment. POPs such as polychlorinated biphenyls (PCBs), hexachlorobenzene (HCB) and dichlorodiphenyltrichloroethane (DDT) have been classified as carcinogenic to humans and animals. Due to their resistance to biodegradation humans are still exposed to these compounds worldwide. We aim to evaluate the miRNA and transcriptomic response of a human population exposed to POPs. The miRNA and transcriptomic response was measured in blood of healthy subjects by microarray technology and associated with the serum concentrations of six PCB congeners, DDE (a common DDT metabolite), and HCB. A total of 93 miRNA levels appeared significantly associated with the POP-exposure (FDR < 0.05). The miRNA profile includes four tumor suppressor miRNAs, namely miR-193a-3p, miR-152, miR-31-5p and miR-34a-5p. Integration of the miRNA profile with the transcriptome profile suggests an interaction with oncogenes such as MYC, CCND1, BCL2 and VEGFA. We have shown that exposure to POPs is associated with human miRNA and transcriptomic responses. The identified miRNAs and target genes are related to various types of cancer and involved in relevant signaling pathways like wnt and p53. Therefore, these miRNAs may have great potential to contribute to biomarker-based environmental health risk assessment.
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| 6. |
- Schillemans, Tessa, et al.
(författare)
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Associations of PFAS-related plasma metabolites with cholesterol and triglyceride concentrations
- 2023
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Ingår i: Environmental Research. - : Elsevier BV. - 0013-9351 .- 1096-0953. ; 216
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Tidskriftsartikel (refereegranskat)abstract
- The wide-spread environmental pollutants per- and polyfluoroalkyl substances (PFAS) have repeatedly been associated with elevated serum cholesterol in humans. However, underlying mechanisms are still unclear. Furthermore, we have previously observed inverse associations with plasma triglycerides. To better understand PFAS-induced effects on lipid pathways we investigated associations of PFAS-related metabolite features with plasma cholesterol and triglyceride concentrations. We used 290 PFAS-related metabolite features that we previously discovered from untargeted liquid chromatography-mass spectometry metabolomics in a case-control study within the Swedish Västerbotten Intervention Programme cohort. Herein, we studied associations of these PFAS-related metabolite features with plasma cholesterol and triglyceride concentrations in plasma samples from 187 healthy control subjects collected on two occasions between 1991 and 2013. The PFAS-related features did not associate with cholesterol, but 50 features were associated with triglycerides. Principal component analysis on these features indicated that one metabolite pattern, dominated by glycerophospholipids, correlated with longer chain PFAS and associated inversely with triglycerides (both cross-sectionally and prospectively), after adjustment for confounders. The observed time-trend of the metabolite pattern resembled that of the longer chain PFAS, with higher levels during the years 2004–2010. Mechanisms linking PFAS exposures to triglycerides may thus occur via longer chain PFAS affecting glycerophospholipid metabolism. If the results reflect a cause-effect association, as implied by the time-trend and prospective analyses, this may affect the general adult population.
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| 7. |
- Shi, Lin, 1988, et al.
(författare)
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Joint Analysis of Metabolite Markers of Fish Intake and Persistent Organic Pollutants in Relation to Type 2 Diabetes Risk in Swedish Adults
- 2019
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Ingår i: Journal of Nutrition. - : Elsevier BV. - 1541-6100 .- 0022-3166. ; 149:8, s. 1413-1423
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND : There is conflicting evidence regarding the association between fish intake and type 2 diabetes (T2D) incidence, possibly owing to measurement errors in self-reported intake and coexposure to persistent organic pollutants (POPs) present in fish. OBJECTIVE : The aim of this study was to identify plasma metabolites associated with fish intake and to assess their association with T2D risk, independently of POPs, in Swedish adults. METHODS : In a case-control study nested in the Swedish Västerbotten Intervention Programme, fasting plasma samples from 421 matched T2D case-control pairs of men and women aged 30-60 y at baseline and 10-y follow-up samples from a subset of 149 pairs were analyzed using untargeted metabolomics. Moreover, 16 plasma POPs were analyzed for the 149 pairs who had repeated samples available. Fish-related plasma metabolites were identified using multivariate modelling and partial correlation analysis. Reproducibility of metabolites and metabolite patterns, derived via principal component analysis (PCA), was assessed by intraclass correlation. A unique component of metabolites unrelated to POPs was dissected by integrating metabolites and POPs using 2-way orthogonal partial least squares regression. ORs of T2D were estimated using conditional logistic regression. RESULTS : We identified 31 metabolites associated with fish intake that had poor to good reproducibility. A PCA-derived metabolite pattern strongly correlated with fish intake (ρ = 0.37, P < 0.001) but showed no association with T2D risk. Integrating fish-related metabolites and POPs led to a unique metabolite component independent of POPs, which tended to be inversely associated with T2D risk (OR: 0.75; 95% CI: 0.54, 1.02, P = 0.07). This component mainly consisted of metabolites reflecting fatty fish intake. CONCLUSIONS: Our results suggest that fatty fish intake may be beneficial for T2D prevention, after removing the counteractive effects of coexposure to POPs in Swedish adults. Integrating metabolite markers and POP exposures appears a promising approach to advance the understanding of associations between fish intake and T2D incidence.
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| 8. |
- Svensson, Katherine, et al.
(författare)
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Prenatal exposures to mixtures of endocrine disrupting chemicals and children's weight trajectory up to age 5.5 in the SELMA study
- 2021
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Exposure to endocrine disrupting chemicals (EDCs) may impact early growth, although information is limited on exposure to combination of multiple EDCs. We aimed to evaluate the effect of prenatal exposure to EDC mixtures on birthweight z-scores and childhood weight trajectories. Twenty-six proven and suspected EDCs, were analyzed in prenatal urine and blood samples from 1118 mothers participating in the Swedish Environmental Longitudinal Mother and child Asthma and allergy (SELMA) study. Two growth parameters were estimated from each child's weight trajectory from birth to 5.5 years of age: infant growth spurt rate and age at infant peak growth velocity (PGV). Weighted quantile sum (WQS) regression was used to estimate the mixture effect and identify chemicals of concern. A one-unit increase in the EDC mixture WQS index, was associated with decreased birthweight z-scores of 0.11 (95% CI - 0.16, - 0.06), slower infant growth spurt rate of 0.01 (95% CI - 0.03, - 0.01, on the log(10) scale), and delayed age at infant PGV of 0.15 months (95% CI 0.07, 0.24) after adjusting for potential confounders. Stratified analysis by sex, showed that delayed age at infant PGV was mostly observed in girls with 0.51 months (95% CI 0.26, 0.76). Identified chemicals of concern included perfluorinated alkyl substances (PFAS), Triclosan, phthalates, non-phthalate plasticizers, bisphenols, polycyclic aromatic hydrocarbons, pesticides and PCBs. Prenatal exposure to EDC mixtures was associated with lower birthweight and altered infant weight gain trajectories.
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| 9. |
- Svensson, Katherine, et al.
(författare)
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Prenatal exposures to mixtures of endocrine disrupting chemicals and sex-specific associations with children’s BMI and overweight at 5.5 years of age in the SELMA study
- 2023
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Ingår i: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 179
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Tidskriftsartikel (refereegranskat)abstract
- Background: Prenatal exposure to mixtures of endocrine disrupting chemicals (EDC) has the potential to disrupt human metabolism. Prenatal periods are especially sensitive as many developmental processes are regulated by hormones. Prenatal exposure to EDCs has inconsistently been associated with children’s body mass index (BMI) and obesity. The objective of this study was to investigate if prenatal exposure to a mixture of EDCs was associated with children’s BMI and overweight (ISO-BMI ≥ 25) at 5.5 years of age, and if there were sex-specific effects. Methods: A total of 1,105 mother–child pairs with complete data on prenatal EDCs concentrations (e.g., phthalates, non-phthalate plasticizers, phenols, PAH, pesticides, PFAS, organochlorine pesticides, and PCBs), children’s measured height and weight, and selected covariates in the Swedish Environmental Longitudinal, Mother and child, Asthma and allergy (SELMA) study were included in this analysis. The mixture effect of EDCs with children’s BMI and overweight was assessed using WQS regression with 100 repeated holdouts. A positively associated WQS index with higher BMI and odds of overweight was derived. Models with interaction term and stratified weights by sex was applied in order to evaluate sex-specific associations. Results: A significant WQS*sex interaction term was identified and associations for boys and girls were in opposite directions. Higher prenatal exposure to a mixture of EDCs was associated with lower BMI (Mean β = -0.19, 95%CI: −0.40, 0.01) and lower odds of overweight (Mean OR = 0.72, 95%CI: 0.48, 1.04) among girls with borderline significance. However, the association among boys did not reach statistical significance. Among girls, the possible chemicals of concern were MEP, 2-OHPH, BPF, BPS, DPP and PFNA. Conclusion: Prenatal exposure to a mixture of EDCs was associated with lower BMI and overweight among girls, and non-significant associations among boys. Chemicals of concern for girls included phthalates, non-phthalate plasticizers, bisphenols, PAHs, and PFAS.
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| 10. |
- Tanner, Eva M, et al.
(författare)
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Early prenatal exposure to suspected endocrine disruptor mixtures is associated with lower IQ at age seven
- 2020
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Ingår i: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 134, s. 1-11
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Tidskriftsartikel (refereegranskat)abstract
- Background: Endocrine disrupting chemicals (EDCs) are xenobiotics with the ability to interfere with hormone action, even at low levels. Prior environmental epidemiology studies link numerous suspected EDCs, including phthalates and bisphenol A (BPA), to adverse neurodevelopmental outcomes. However, results for some chemicals were inconsistent and most assessed one chemical at a time.Objectives: To evaluate the overall impact of prenatal exposure to an EDC mixture on neurodevelopment in school-aged children, and identify chemicals of concern while accounting for co-exposures.Methods: Among 718 mother-child pairs from the Swedish Environmental Longitudinal, Mother and child, Asthma and allergy study (SELMA) study, we used Weighted Quantile Sum (WQS) regression to assess the association between 26 EDCs measured in 1st trimester urine or blood, with Wechsler Intelligence Scale for Children (IV) Intelligence Quotient (IQ) scores at age 7 years. Models were adjusted for child sex, gestational age, mother's education, mother's IQ (RAVEN), weight, and smoking status. To evaluate generalizability, we conducted repeated holdout validation, a machine learning technique.ResultsUsing repeated holdout validation, IQ scores were 1.9-points (CI = −3.6, −0.2) lower among boys for an inter-quartile-range (IQR) change in the WQS index. BPF made the largest contribution to the index with a weight of 14%. Other chemicals of concern and their weights included PBA (9%), TCP (9%), MEP (6%), MBzP (4%), PFOA (6%), PFOS (5%), PFHxS (4%), Triclosan (5%), and BPA (4%). While we did observe an inverse association between EDCs and IQ among all children when training and testing the WQS index estimate on the full dataset, these results were not robust to repeated holdout validation.Conclusion: Among boys, early prenatal exposure to EDCs was associated with lower intellectual functioning at age 7. We identified bisphenol F as the primary chemical of concern, suggesting that the BPA replacement compound may not be any safer for children. Future studies are needed to confirm the potential neurotoxicity of replacement analogues.
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