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Feldreich, T., Nowak, C., Fall, T., Carlsson, A. C., Carrero, J.-J., Ripsweden, J., . . . Arnlov, J. (2019). Circulating proteins as predictors of cardiovascular mortality in end-stage renal disease. JN. Journal of Nephrology (Milano. 1992), 32(1), 111-119
Open this publication in new window or tab >>Circulating proteins as predictors of cardiovascular mortality in end-stage renal disease
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2019 (English)In: JN. Journal of Nephrology (Milano. 1992), ISSN 1121-8428, E-ISSN 1724-6059, Vol. 32, no 1, p. 111-119Article in journal (Refereed) Published
Abstract [en]

Proteomic profiling of end-stage renal disease (ESRD) patients could lead to improved risk prediction and novel insights into cardiovascular disease mechanisms. Plasma levels of 92 cardiovascular disease-associated proteins were assessed by proximity extension assay (Proseek Multiplex CVD-1, Olink Bioscience, Uppsala, Sweden) in a discovery cohort of dialysis patients, the Mapping of Inflammatory Markers in Chronic Kidney disease cohort [MIMICK; n=183, 55% women, mean age 63years, 46 cardiovascular deaths during follow-up (mean 43months)]. Significant results were replicated in the incident and prevalent hemodialysis arm of the Salford Kidney Study [SKS dialysis study, n=186, 73% women, mean age 62years, 45 cardiovascular deaths during follow-up (mean 12months)], and in the CKD5-LD-RTxcohort with assessments of coronary artery calcium (CAC)-score by cardiac computed tomography (n=89, 37% women, mean age 46years).

Results

In age and sex-adjusted Cox regression in MIMICK, 11 plasma proteins were nominally associated with cardiovascular mortality (in order of significance: Kidney injury molecule-1 (KIM-1), Matrix metalloproteinase-7, Tumour necrosis factor receptor 2, Interleukin-6, Matrix metalloproteinase-1, Brain-natriuretic peptide, ST2 protein, Hepatocyte growth factor, TNF-related apoptosis inducing ligand receptor-2, Spondin-1, and Fibroblast growth factor 25). Only plasma KIM-1 was associated with cardiovascular mortality after correction for multiple testing, but also after adjustment for dialysis vintage, cardiovascular risk factors and inflammation (hazard ratio) per standard deviation (SD) increase 1.84, 95% CI 1.26-2.69, p=0.002. Addition of KIM-1, or nine of the most informative proteins to an established risk-score (modified AROii CVM-score) improved discrimination of cardiovascular mortality risk from C=0.777 to C=0.799 and C=0.823, respectively. In the SKS dialysis study, KIM-1 predicted cardiovascular mortality in age and sex adjusted models (hazard ratio per SD increase 1.45, 95% CI 1.03-2.05, p=0.034) and higher KIM-1 was associated with higher CACscores in the CKD5-LD-RTx-cohort.

Conclusions

Our proteomics approach identified plasma KIM-1 as a risk marker for cardiovascular mortality and coronary artery calcification in three independent ESRD-cohorts. The improved risk prediction for cardiovascular mortality by plasma proteomics merit further studies.

Keywords
CVD, ESRD, Proteomics
National Category
Urology and Nephrology
Identifiers
urn:nbn:se:uu:diva-378193 (URN)10.1007/s40620-018-0556-5 (DOI)000458699800013 ()30499038 (PubMedID)
Funder
Swedish Research CouncilEU, Horizon 2020, 722609EU, Horizon 2020, 634869Swedish Heart Lung FoundationSwedish Society for Medical Research (SSMF)
Available from: 2019-03-04 Created: 2019-03-04 Last updated: 2019-03-04Bibliographically approved
Landegren, N., Rosen, L. B., Freyhult, E., Eriksson, D., Fall, T., Smith, G., . . . Kampe, O. (2019). Comment on 'AIRE-deficient patients harbor unique high-affinity disease-ameliorating autoantibodies'. eLIFE, 8, Article ID e43578.
Open this publication in new window or tab >>Comment on 'AIRE-deficient patients harbor unique high-affinity disease-ameliorating autoantibodies'
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2019 (English)In: eLIFE, E-ISSN 2050-084X, Vol. 8, article id e43578Article in journal, Editorial material (Other academic) Published
Abstract [en]

The AIRE gene plays a key role in the development of central immune tolerance by promoting thymic presentation of tissue-specific molecules. Patients with AIRE-deficiency develop multiple autoimmune manifestations and display autoantibodies against the affected tissues. In 2016 it was reported that: i) the spectrum of autoantibodies in patients with AIRE-deficiency is much broader than previously appreciated; ii) neutralizing autoantibodies to type I interferons (IFNs) could provide protection against type 1 diabetes in these patients (Meyer et al., 2016). We attempted to replicate these new findings using a similar experimental approach in an independent patient cohort, and found no evidence for either conclusion.

Place, publisher, year, edition, pages
ELIFE SCIENCES PUBLICATIONS LTD, 2019
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:uu:diva-390333 (URN)10.7554/eLife.43578 (DOI)000473150200001 ()31244471 (PubMedID)
Funder
Swedish Research Council FormasSwedish Research CouncilKnut and Alice Wallenberg FoundationNovo NordiskSwedish Society for Medical Research (SSMF)
Available from: 2019-08-09 Created: 2019-08-09 Last updated: 2019-08-09Bibliographically approved
Mubanga, M., Byberg, L., Egenvall, A., Sundström, J., Magnusson, P. K., Ingelsson, E. & Fall, T. (2019). Dog ownership and Cardiovascular Risk Factors: a nationwide prospective register-based cohort study. BMJ Open, 9, Article ID e023447.
Open this publication in new window or tab >>Dog ownership and Cardiovascular Risk Factors: a nationwide prospective register-based cohort study
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2019 (English)In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 9, article id e023447Article in journal (Refereed) Submitted
Abstract [en]

Objective To study the association between dog ownership and cardiovascular risk factors.

Design A nationwide register–based cohort study and a cross-sectional study in a subset.

Setting A cohort of 2 026 865 participants was identified from the Register of the Total Population and linked to national registers for information on dog ownership, prescribed medication, hospital admissions, education level, income and country of birth. Participants were followed from 1 October, 2006, to the end of the study on 31 December, 2012, assessing medication for a cardiovascular risk factor, emigration and death. Cross-sectional associations were further assessed in 10 110 individuals from the TwinGene study with additional adjustment for professional level, employment status, Charlson comorbidity index, disability and tobacco use.

Participants All Swedish residents aged 45–80 years on 1 October, 2006.

Main outcome measures Initiation of medication for hypertension, dyslipidaemia and diabetes mellitus.

Results After adjustment for confounders, the results indicated slightly higher likelihood of initiating antihypertensive (HR, 1.02; 95% CI, 1.01 to 1.03) and lipid-lowering treatment (HR, 1.02; 95% CI, 1.01 to 1.04) in dog owners than in non-owners, particularly among those aged 45–60 years and in those owning mixed breed or companion/toy breed dogs. No association of dog ownership with initiation of treatment for diabetes was found in the overall analysis (HR, 0.98; 95% CI, 0.95 to 1.01). Sensitivity analyses in the TwinGene cohort indicated confounding of the association between dog ownership and prevalent treatment for hypertension, dyslipidaemia and diabetes mellitus, respectively, from factors not available in the national cohort, such as employment status and non cardiovascularchronic disease status.

Conclusions In this large cohort study, dog ownership was associated with a minimally higher risk of initiation of treatment for hypertension and dyslipidaemia implying that the previously reported lower risk of cardiovascular mortality among dog owners in this cohort is not explained by reduced hypertension and dyslipidaemia. These observations may suffer from residual confounding despite access to multiple important covariates, and future studies may add valuable information.

Keywords
cardiovascular risk, hypertension, dog ownership, diabetes, registers
National Category
Cardiac and Cardiovascular Systems Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:uu:diva-357625 (URN)10.1136/bmjopen-2018-023447 (DOI)000471144900063 ()30850401 (PubMedID)
Funder
Swedish Research Council, 2017-00641Swedish Research Council Formas, 2013-1673Göran Gustafsson Foundation for Research in Natural Sciences and Medicine
Available from: 2018-08-19 Created: 2018-08-19 Last updated: 2019-07-22Bibliographically approved
Fall, T., Kuja-Halkola, R., Dobney, K., Westgarth, C. & Magnusson, P. K. E. (2019). Evidence of large genetic influences on dog ownership in the Swedish Twin Registry has implications for understanding domestication and health associations. Scientific Reports, 9, Article ID 7554.
Open this publication in new window or tab >>Evidence of large genetic influences on dog ownership in the Swedish Twin Registry has implications for understanding domestication and health associations
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2019 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 7554Article in journal (Refereed) Published
Abstract [en]

Dogs were the first domesticated animal and, according to the archaeological evidence, have had a close relationship with humans for at least 15,000 years. Today, dogs are common pets in our society and have been linked to increased well-being and improved health outcomes in their owners. A dog in the family during childhood is associated with ownership in adult life. The underlying factors behind this association could be related to experiences or to genetic influences. We aimed to investigate the heritability of dog ownership in a large twin sample including all twins in the Swedish Twin Registry born between 1926 and 1996 and alive in 2006. Information about dog ownership was available from 2001 to 2016 from national dog registers. The final data set included 85,542 twins from 50,507 twin pairs with known zygosity, where information on both twins were available in 35,035 pairs. Structural equation modeling was performed to estimate additive genetic effects (the heritability), common/shared environmental, and unique/non-shared environmental effects. We found that additive genetic factors largely contributed to dog ownership, with heritability estimated at 57% for females and 51% for males. An effect of shared environmental factors was only observed in early adulthood. In conclusion, we show a strong genetic contribution to dog ownership in adulthood in a large twin study. We see two main implications of this finding: (1) genetic variation may have contributed to our ability to domesticate dogs and other animals and (2) potential pleiotropic effects of genetic variation affecting dog ownership should be considered in studies examining health impacts of dog ownership.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP, 2019
National Category
Genetics
Identifiers
urn:nbn:se:uu:diva-385976 (URN)10.1038/s41598-019-44083-9 (DOI)000468171100049 ()31101867 (PubMedID)
Funder
Swedish Research CouncilSwedish Heart Lung Foundation
Note

The Swedish Twin Registry is managed by Karolinska Institutet and receives funding through the Swedish Research Council under the grant no 2017-00641.

Available from: 2019-06-18 Created: 2019-06-18 Last updated: 2019-06-18Bibliographically approved
Salihovic, S., Fall, T., Ganna, A., Broeckling, C. D., Prenni, J. E., Hyötyläinen, T., . . . Lind, L. (2019). Identification of metabolic profiles associated with human exposure to perfluoroalkyl substances.. Journal of Exposure Science and Environmental Epidemiology, 29(2), 196-205
Open this publication in new window or tab >>Identification of metabolic profiles associated with human exposure to perfluoroalkyl substances.
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2019 (English)In: Journal of Exposure Science and Environmental Epidemiology, ISSN 1559-0631, E-ISSN 1559-064X, Vol. 29, no 2, p. 196-205Article in journal (Refereed) Published
Abstract [en]

Recent epidemiological studies suggest that human exposure to perfluoroalkyl substances (PFASs) may be associated with type 2 diabetes and other metabolic phenotypes. To gain further insights regarding PFASs exposure in humans, we here aimed to characterize the associations between different PFASs and the metabolome. In this cross-sectional study, we investigated 965 individuals from Sweden (all aged 70 years, 50% women) sampled in 2001-2004. PFASs were analyzed in plasma using isotope-dilution ultra-pressure liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS). Non-target metabolomics profiling was performed in plasma using UPLC coupled to time-of-flight mass spectrometry (UPLC-QTOFMS) operated in positive electrospray mode. Multivariate linear regression analysis was used to investigate associations between circulating levels of PFASs and metabolites. In total, 15 metabolites, predominantly from lipid pathways, were associated with levels of PFASs following adjustment for sex, smoking, exercise habits, education, energy, and alcohol intake, after correction for multiple testing. Perfluorononanoic acid (PFNA) and perfluoroundecanoic acid (PFUnDA) were strongly associated with multiple glycerophosphocholines and fatty acids including docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA). We also found that the different PFASs evaluated were associated with distinctive metabolic profiles, suggesting potentially different biochemical pathways in humans.

Keywords
Epidemiology, Metabolomics, PFOA, PFOS, Perfluoroalkyl substances, XCMS
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:uu:diva-366082 (URN)10.1038/s41370-018-0060-y (DOI)000459048700007 ()30185940 (PubMedID)
Available from: 2018-11-16 Created: 2018-11-16 Last updated: 2019-08-01Bibliographically approved
Fall, T., Hedman, A., Pershagen, G., Andolf, E., Almqvist, C., Helmersson-Karlqvist, J. & Larsson, A. (2019). Reference Intervals for Fecal Calprotectin in Pregnant Women Using a Particle Enhanced Turbidimetric Assay. Clinical Laboratory, 65(7), 1293-1297
Open this publication in new window or tab >>Reference Intervals for Fecal Calprotectin in Pregnant Women Using a Particle Enhanced Turbidimetric Assay
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2019 (English)In: Clinical Laboratory, ISSN 1433-6510, Vol. 65, no 7, p. 1293-1297Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Fecal calprotectin is widely used as a marker for inflammatory bowel diseases (IBD). IBD often affects women during their reproductive years, but there are no established reference intervals during pregnancy. The aim of the present study was to define reference values during pregnancy and in the postpartum period to allow comparisons between patient results and reference values.

METHODS: Fecal samples were collected from 84 healthy females during pregnancy week 26 to 28 and a second sample was collected six months after delivery. The samples were weighed, extracted, and centrifugated to remove debris. The extracted samples were then analyzed on a chemistry analyzer using a particle enhanced turbidimetric immunoassay reagent.

RESULTS: The calculated reference interval during pregnancy was < 127 μg/g (90% confidence interval, 90 - 164 μg/g) and the corresponding reference interval during the postpartum period was < 143 μg/g (60 - 226 μg/g). There were no significant statistical differences between F-calprotectin values analyzed at the two sampling times.

CONCLUSIONS: The reference values are slightly higher than the cutoff values of 50 - 100 μg/g often used as General cutoff for fecal calprotectin.

Keywords
biological markers, calprotectin, feces, inflammatory bowel diseases, reference interval, pregnancy
National Category
Clinical Laboratory Medicine
Identifiers
urn:nbn:se:uu:diva-389529 (URN)10.7754/Clin.Lab.2019.190104 (DOI)000475700400020 ()31307176 (PubMedID)
Funder
Swedish Heart Lung Foundation, 20150429Knut and Alice Wallenberg FoundationSwedish Research Council, 2015-03477VinnovaErik, Karin och Gösta Selanders FoundationGöran Gustafsson Foundation for promotion of scientific research at Uppala University and Royal Institute of TechnologySwedish Research Council, 340-2013-5867Swedish Asthma and Allergy AssociationStockholm County CouncilForte, Swedish Research Council for Health, Working Life and Welfare
Available from: 2019-07-17 Created: 2019-07-17 Last updated: 2019-08-23Bibliographically approved
Stenemo, M., Ganna, A., Salihovic, S., Nowak, C., Sundström, J., Giedraitis, V., . . . Fall, T. (2019). The metabolites urobilin and sphingomyelin (30:1) are associated with incident heart failure in the general population. ESC Heart Failure, 6(4), 764-773
Open this publication in new window or tab >>The metabolites urobilin and sphingomyelin (30:1) are associated with incident heart failure in the general population
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2019 (English)In: ESC Heart Failure, E-ISSN 2055-5822, Vol. 6, no 4, p. 764-773Article in journal (Refereed) Published
Abstract [en]

Aims: We aimed to investigate whether metabolomic profiling of blood can lead to novel insights into heart failure pathogenesis or improved risk prediction.

Methods: Mass spectrometry-based metabolomic profiling was performed in plasma or serum samples from three community-based cohorts without heart failure at baseline (total n=3,924; 341 incident heart failure events, median follow-up ranging from 4.6 to 13.9 years). Cox proportional hazards models were applied to assess the association of each of the 206 identified metabolites with incident heart failure in the discovery cohorts Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS, n=920) and Uppsala Longitudinal Study of Adult Men (ULSAM, n=1,121). Replication was undertaken in the independent cohort TwinGene (n=1,797). We also assessed whether metabolites could improve the prediction of heart failure beyond established risk factors (age, sex, body mass index, low-density lipoprotein- and high-density lipoprotein-cholesterol, triglycerides, lipid medication, diabetes, systolic and diastolic blood pressure, blood pressure medication, glomerular filtration rate, smoking status, and myocardial infarction prior to or during follow-up).

Results: Higher circulating urobilin and lower sphingomyelin (30:1) were associated with incident heart failure in age- and sex-adjusted models in the discovery and replication sample. The hazard ratio (HR) for urobilin in the replication cohort was estimated to 1.29 per SD unit, 95% confidence interval (CI) 1.03-1.63) and for sphingomyelin (30:1) to 0.72 (95% CI 0.58-0.89). Results remained similar after further adjustment for established heart failure risk factors in meta-analyses of all three cohorts. Urobilin concentrations were inversely associated with left ventricular ejection fraction at baseline in the PIVUS cohort (β= -0.70 (95% CI -1.03-(-0.38)). No improvement in risk prediction was observed when adding the two top metabolites (C-index 0.787 (95% CI 0.752-0.823)) or nine Lasso-selected metabolites (0.790 (95% CI 0.754-0.826)) to a modified Atherosclerosis Risk in Communities (ARIC) heart failure risk score model (0.780 (95% CI 0.745-0.816)).

Conclusions: Our metabolomics study identified associations of circulating levels of the heme breakdown product urobilin, and sphingomyelin (30:1), a cell membrane component involved in signal transduction and apoptosis, with incident heart failure.

National Category
Clinical Medicine Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-381229 (URN)10.1002/ehf2.12453 (DOI)000478602300020 ()31148414 (PubMedID)
Funder
Swedish Research Council, 2017-00641Swedish Research Council, 2012-02215Swedish Heart Lung FoundationEU, Horizon 2020, 634869
Available from: 2019-04-05 Created: 2019-04-05 Last updated: 2019-09-24Bibliographically approved
Beijer, K., Sundström, J., Arnlöv, J., Fall, T., Ingelsson, E. & Lind, L. (2018). A targeted proteomic profile of prevalent diabetes in a population-based sample. Paper presented at 54th Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD), OCT 01-05, 2018, Berlin, GERMANY. Diabetologia, 61, S252-S252
Open this publication in new window or tab >>A targeted proteomic profile of prevalent diabetes in a population-based sample
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2018 (English)In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 61, p. S252-S252Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Springer, 2018
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-367122 (URN)000443556003105 ()
Conference
54th Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD), OCT 01-05, 2018, Berlin, GERMANY
Available from: 2018-11-30 Created: 2018-11-30 Last updated: 2018-11-30Bibliographically approved
Figarska, S. M., Gustafsson, S., Sundström, J., Ärnlöv, J., Mälarstig, A., Elmstahl, S., . . . Ingelsson, E. (2018). Associations of Circulating Protein Levels With Lipid Fractions in the General Population. Arteriosclerosis, Thrombosis and Vascular Biology, 38(10), 2505-2518
Open this publication in new window or tab >>Associations of Circulating Protein Levels With Lipid Fractions in the General Population
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2018 (English)In: Arteriosclerosis, Thrombosis and Vascular Biology, ISSN 1079-5642, E-ISSN 1524-4636, Vol. 38, no 10, p. 2505-2518Article in journal (Refereed) Published
Abstract [en]

Objective: Revealing patterns of associations between circulating protein and lipid levels could improve biological understanding of cardiovascular disease (CVD). In this study, we investigated the associations between proteins related to CVD and triglyceride (TG), total cholesterol, LDL (low-density lipoprotein), and HDL (high-density lipoprotein) cholesterol levels in individuals from the general population.

Approach and Results: We measured plasma protein levels using the Olink ProSeek CVD I or II+III arrays and analyzed 57 proteins available in 3 population-based cohorts: EpiHealth (n=2029; 52% women; median age, 61 years), PIVUS (Prospective Study of the Vasculature in Uppsala Seniors; n=790; 51% women; all aged 70 years), and ULSAM (Uppsala Longitudinal Study of Adult Men; n=551; all men aged 77 years). A discovery analysis was performed in EpiHealth in a regression framework (adjusted for sex, age, body mass index, smoking, glucose levels, systolic blood pressure, blood pressure medication, diabetes mellitus medication, and CVD history), and associations with false discovery rate <0.05 were further tested in PIVUS and ULSAM, where a P value of 0.05 was considered a successful replication (validation false discovery rate of 0.1%). We used summary statistics from a genome-wide association study on each protein biomarker (meta-analysis of EpiHealth, PIVUS, ULSAM, and IMPROVE [Carotid Intima-Media Thickness and IMT-Progression as Predictors of Vascular Events in a High-Risk European Population]) and publicly available data from Global Lipids Genetics Consortium to perform Mendelian randomization analyses to address possible causality of protein levels. Of 57 tested proteins, 42 demonstrated an association with at least 1 lipid fraction; 35 were associated with TG, 15 with total cholesterol, 9 with LDL cholesterol, and 24 with HDL cholesterol. Among these associations, we found KIM-1 (kidney injury molecule-1), TNFR (TNF [tumor necrosis factor] receptor) 1 and 2, TRAIL-R2 (TRAIL [TNF-related apoptosis-inducing ligand] receptor 2), and RETN (resistin) to be associated with all 4 lipid fractions. Further, 15 proteins were related to both TG and HDL cholesterol in a consistent and biologically expected manner, that is, higher TG and lower HDL cholesterol or vice versa. Another common pattern of associations was concomitantly higher TG, total cholesterol, and LDL cholesterol, which is associated with higher CVD risk. We did not find evidence of causal links for protein levels.

Conclusions: Our comprehensive analysis of plasma proteins and lipid fractions of 3370 individuals from the general population provides new information about lipid metabolism.

Place, publisher, year, edition, pages
LIPPINCOTT WILLIAMS & WILKINS, 2018
Keywords
cholesterol, humans, proteomics, triglycerides
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-363206 (URN)10.1161/ATVBAHA.118.311440 (DOI)000445750500026 ()
Funder
Knut and Alice Wallenberg Foundation, 2013.0126
Available from: 2018-10-18 Created: 2018-10-18 Last updated: 2018-10-18Bibliographically approved
Salihovic, S., Stubleski, J., Kärrman, A., Larsson, A., Fall, T., Lind, L. & Lind, P. M. (2018). Changes in markers of liver function in relation to changes in perfluoroalkyl substances - A longitudinal study. Environment International, 117, 196-203
Open this publication in new window or tab >>Changes in markers of liver function in relation to changes in perfluoroalkyl substances - A longitudinal study
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2018 (English)In: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 117, p. 196-203Article in journal (Refereed) Published
Abstract [en]

Background: While it is known that perfluoroalkyl substances (PFASs) induce liver toxicity in experimental studies, the evidence of an association in humans is inconsistent.

Objective: The main aim of the present study was to examine the association of PFAS concentrations and markers of liver function using panel data.

Methods: We investigated 1002 individuals from Sweden (50% women) at ages 70, 75 and 80 in 2001-2014. Eight PFASs were measured in plasma using isotope dilution ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS). Bilirubin and hepatic enzymes alanine aminotransferase (ALT), alkaline phosphatase (ALP), and gamma-glutamyltransferase (GGT) were determined in serum using an immunoassay methodology. Mixed-effects linear regression models were used to examine the relationship between the changes in markers of liver function and changes in PFAS levels.

Results: The changes in majority of PFAS concentrations were positively associated with the changes in activity of ALT, ALP, and GGT and inversely associated with the changes in circulating bilirubin after adjustment for gender and the time-updated covariates LDL- and HDL-cholesterol, serum triglycerides, BMI, statin use, smoking, fasting glucose levels and correction for multiple testing. For example, changes in perfluorononanoic acid (PFNA) were associated with the changes liver function markers beta(BILIRUBIN) = -1.56, 95% confidence interval (CI) -1.93 to -1.19, beta(ALT)= 0.04, 95% CI 0.03-0.06, and beta(ALP)= 0.11, 95% CI 0.06-0.15.

Conclusion: Our longitudinal assessment established associations between changes in markers of liver function and changes in plasma PFAS concentrations. These findings suggest a relationship between low-dose background PFAS exposure and altered liver function in the general population.

Place, publisher, year, edition, pages
PERGAMON-ELSEVIER SCIENCE LTD, 2018
Keywords
Epidemiology, Liver function markers, PFAS, ALT, Bilirubin, PFNA
National Category
Occupational Health and Environmental Health
Identifiers
urn:nbn:se:uu:diva-361035 (URN)10.1016/j.envint.2018.04.052 (DOI)000436573400023 ()29754000 (PubMedID)
Funder
Swedish Research Council Formas, 2007-2047Swedish Research Council Formas, 2013-478Swedish Research Council Formas, 2015-756
Available from: 2018-09-21 Created: 2018-09-21 Last updated: 2018-09-21Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0003-2071-5866

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