| 1. |
- 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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| 2. |
- Schillemans, Tessa, et al.
(författare)
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Omics signatures linking persistent organic pollutants to cardiovascular disease in the Swedish mammography cohort
- 2024
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 58:2, s. 1036-1047
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Tidskriftsartikel (refereegranskat)abstract
- Cardiovascular disease (CVD) development may be linked to persistent organic pollutants (POPs), including organochlorine compounds (OCs) and perfluoroalkyl and polyfluoroalkyl substances (PFAS). To explore underlying mechanisms, we investigated metabolites, proteins, and genes linking POPs with CVD risk. We used data from a nested case-control study on myocardial infarction (MI) and stroke from the Swedish Mammography Cohort - Clinical (n = 657 subjects). OCs, PFAS, and multiomics (9511 liquid chromatography-mass spectrometry (LC-MS) metabolite features; 248 proteins; 8110 gene variants) were measured in baseline plasma. POP-related omics features were selected using random forest followed by Spearman correlation adjusted for confounders. From these, CVD-related omics features were selected using conditional logistic regression. Finally, 29 (for OCs) and 12 (for PFAS) unique features associated with POPs and CVD. One omics subpattern, driven by lipids and inflammatory proteins, associated with MI (OR = 2.03; 95% CI = 1.47; 2.79), OCs, age, and BMI, and correlated negatively with PFAS. Another subpattern, driven by carnitines, associated with stroke (OR = 1.55; 95% CI = 1.16; 2.09), OCs, and age, but not with PFAS. This may imply that OCs and PFAS associate with different omics patterns with opposite effects on CVD risk, but more research is needed to disentangle potential modifications by other factors.
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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. |
- 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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