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Salihovic, Samira
Publications (10 of 35) Show all publications
Lind, L., Salihovic, S., Ganna, A., Sundström, J., Broeckling, C. D., Magnusson, P. K., . . . Arnlov, J. (2020). A Multi-Cohort Metabolomics Analysis Discloses Sphingomyelin (32:1) Levels to be Inversely Related to Incident Ischemic Stroke. Journal of Stroke & Cerebrovascular Diseases, 29(2), Article ID 104476.
Open this publication in new window or tab >>A Multi-Cohort Metabolomics Analysis Discloses Sphingomyelin (32:1) Levels to be Inversely Related to Incident Ischemic Stroke
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2020 (English)In: Journal of Stroke & Cerebrovascular Diseases, ISSN 1052-3057, E-ISSN 1532-8511, Vol. 29, no 2, article id 104476Article in journal (Refereed) Published
Abstract [en]

Background and Purpose:

To search for novel pathophysiological pathways related to ischemic stroke using a metabolomics approach.

Methods:

We identified 204 metabolites in plasma by liquid chromatography mass spectrometry in 3 independent population-based samples (TwinGene, Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) and Uppsala Longitudinal Study of Adult Men). TwinGene was used for discovery and the other 2 samples were meta-analyzed as replication. In PIVUS, traditional cardiovascular (CV) risk factors, multiple markers of subclinical CV disease, markers of coagulation/fibrinolysis were measured and analyzed in relation to top metabolites.

Results:

In TwinGene (177 incident cases, median follow-up 4.3 years), levels of 28 metabolites were associated with incident ischemic stroke at a false discover rate (FDR) of 5%. In the replication (together 194 incident cases, follow-up 10 and 12 years, respectively), only sphingomyelin (32:1) was significantly associated (HR.69 per SD change, 95% CI.57-0.83, P value = .00014; FDR <5%) when adjusted for systolic blood pressure, diabetes, smoking, low density lipoportein (LDL)- and high density lipoprotein (HDL), body mass index (BMI) and atrial fibrillation. In PIVUS, sphingomyelin (32:1) levels were significantly related to both LDL- and HDL-cholesterol in a positive fashion, and to serum triglycerides, BMI and diabetes in a negative fashion. Furthermore, sphingomyelin (32:1) levels were related to vasodilation in the forearm resistance vessels, and inversely to leukocyte count (P < .0069 and .0026, respectively).

Conclusions:

An inverse relationship between sphingomyelin (32:1) and incident ischemic stroke was identified, replicated, and characterized. A possible protective role for sphingomyelins in stroke development has to be further investigated in additional experimental and clinical studies.

Keywords
Epidemiology, metabolomics, stroke, risk factor
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-402618 (URN)10.1016/j.jstrokecerebrovasdis.2019.104476 (DOI)000505793800001 ()31806450 (PubMedID)
Funder
Swedish Research CouncilSwedish Heart Lung Foundation
Available from: 2020-01-17 Created: 2020-01-17 Last updated: 2020-01-17Bibliographically approved
Jayasinghe, S., Lind, L., Salihovic, S., Larsson, A. & Lind, P. M. (2019). DDT and its metabolites could contribute to the aetiology of chronic kidney disease of unknown aetiology (CKDu) and more studies are a priority. Science of the Total Environment, 649, 1638-1639
Open this publication in new window or tab >>DDT and its metabolites could contribute to the aetiology of chronic kidney disease of unknown aetiology (CKDu) and more studies are a priority
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2019 (English)In: Science of the Total Environment, ISSN 0048-9697, E-ISSN 1879-1026, Vol. 649, p. 1638-1639Article in journal (Refereed) Published
Place, publisher, year, edition, pages
Elsevier, 2019
Keywords
Chronic kidney disease, DDE, DDT
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:uu:diva-363386 (URN)10.1016/j.scitotenv.2018.09.116 (DOI)000446076500155 ()30227991 (PubMedID)
Available from: 2018-10-17 Created: 2018-10-17 Last updated: 2018-12-04Bibliographically 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
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
Stubleski, J., Kukucka, P., Salihovic, S., Lind, P. M., Lind, L. & Kärrman, A. (2018). A method for analysis of marker persistent organic pollutants in low-volume plasma and serum samples using 96-well plate solid phase extraction. Journal of Chromatography A, 1546, 18-27, Article ID S0021-9673(18)30253-X.
Open this publication in new window or tab >>A method for analysis of marker persistent organic pollutants in low-volume plasma and serum samples using 96-well plate solid phase extraction
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2018 (English)In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1546, p. 18-27, article id S0021-9673(18)30253-XArticle in journal (Refereed) Published
Abstract [en]

The objective of this study was to develop and validate a 96-well plate solid phase extraction method for analysis of 23 lipophilic persistent organic pollutants (POPs) in low-volume plasma and serum samples which is applicable for biomonitoring and epidemiological studies. The analysis of selected markers for internal exposure: 16 polychlorinated biphenyls (PCBs), 5 organochlorine pesticides (OCPs), octachlorinated dibenzo-p-dioxin (OCDD), and polybrominated diphenylether 47 (BDE 47) was evaluated by comparing two SPE sorbents and GC-HRMS or GC-MS/MS detection. The final method extracted 23 POPs from 150 μL of serum and plasma using a 96-well extraction plate containing 60 mg Oasis HLB sorbent per well prior to GC-HRMS magnetic sector analysis. The extraction method was applied to 40 plasma samples collected for an epidemiological study. The recovery of selected POPs ranged from 31% to 63% (n = 48), and detection limits ranged from 2.2 to 45 pg/mL for PCBs, 4.2 to 167 pg/mL for OCPs, 7.8 pg/mL for OCDD and 6.1 pg/mL for BDE 47. This method showed good precision with relative standard deviations of selected POP concentrations in quality control samples (n = 48) ranging from 11% to 25%. The trueness was determined with standard reference material serum (n = 48) and the deviation from certified values ranged from 1 to 27%. Of the 23 POPs analyzed, 18 were detected in 43% to 100% of plasma samples collected for the epidemiological study. The method showed good robustness with low inter-well plate variation (11-31%) determined by twelve 96-well plate extractions, and can extract 96 samples, including quality controls and procedural blanks in 2-3 days. Comparison with GC-MS/MS analysis showed that similar concentrations (within 0.5% to 30%) of most POPs could be obtained with GC-APCI-MS/MS. Larger deviations were observed for PCB 194 (60%) and trans-nonachlor (43%). The developed method produces accurate concentrations of low-level marker POPs in plasma and serum, providing a suitable high-throughput sample preparation procedure for biomonitoring and epidemiological studies involving large sample size and limited sample volume. GC-HRMS was chosen over GC-MS/MS, however the latter showed promising results, and could be used as an alternative to GC-HRMS analysis for most POPs.

Keywords
APCI-MS/MS, GC-HRMS, High-throughput SPE, Persistent organic pollutants
National Category
Occupational Health and Environmental Health
Identifiers
urn:nbn:se:uu:diva-348564 (URN)10.1016/j.chroma.2018.02.057 (DOI)000430766800003 ()29510870 (PubMedID)
Funder
Swedish Research Council Formas, 216-2013-478
Available from: 2018-04-16 Created: 2018-04-16 Last updated: 2018-06-26Bibliographically 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
Lind, P. M., Salihovic, S., Stubleski, J., Kärrman, A. & Lind, L. (2018). Changes in plasma levels of perfluoroalkyl substances (PFASs) are related to increase in carotid intima-media thickness over 10 years - a longitudinal study. Environmental health, 17, Article ID 59.
Open this publication in new window or tab >>Changes in plasma levels of perfluoroalkyl substances (PFASs) are related to increase in carotid intima-media thickness over 10 years - a longitudinal study
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2018 (English)In: Environmental health, ISSN 1476-069X, E-ISSN 1476-069X, Vol. 17, article id 59Article in journal (Refereed) Published
Abstract [en]

Background: It has previously been reported that the environmental contaminants perfluoroalkyl substances (PFASs) are linked to atherosclerosis in cross-sectional studies. Since cross-sectional studies could be subject to reverse causation, the purpose of this study was to analyze if the longitudinal changes in PFASs during a 10-year follow-up were related to the change in carotid artery intima-media thickness (IMT, ultrasound) during the same period.

Methods: In the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study, 1016 individuals were investigated at age 70; 826 of them were reinvestigated at age 75 and 602 at age 80 years. Eight different PFASs were measured in plasma by ultra-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), and IMT was measured at all three time points. Random-effects mixed regression models were used to examine the associations over time.

Results: IMT increased 0.058 mm during the 10-year period (p <0.0001). Following adjustment for baseline values of PFASs (age 70) and sex, the changes in plasma levels of 6 of the 8 measured PFASs were significantly related to the change in IMT over the 10-year follow-up period in a positive fashion (p <0.0062 using Bonferroni correction for 8 tests). Further adjustment for traditional cardiovascular (CV) risk factors (HDL and LDL cholesterol, smoking, systolic blood pressure, statin use, fasting glucose and serum triglycerides) affected these relationships only marginally.

Conclusion: The change in plasma levels of several PFASs during 10 years was positively related to increase in IMT seen during the same period, giving prospective evidence that PFASs might interfere with the atherosclerotic process.

Place, publisher, year, edition, pages
BMC, 2018
Keywords
Atherosclerosis, Longitudinal, Perfluoroalkyl substances (PFASs), Elderly, Epidemiology, IMT
National Category
Cardiac and Cardiovascular Systems Occupational Health and Environmental Health
Identifiers
urn:nbn:se:uu:diva-360187 (URN)10.1186/s12940-018-0403-0 (DOI)000437299700002 ()29970113 (PubMedID)
Funder
Swedish Research Council Formas, 2007-2047
Available from: 2018-09-13 Created: 2018-09-13 Last updated: 2018-09-13Bibliographically approved
Mobacke, I., Lind, L., Dunder, L., Salihovic, S. & Lind, P. M. (2018). Circulating levels of perfluoroalkyl substances and left ventricular geometry of the heart in the elderly.. Environment International, 115, 295-300
Open this publication in new window or tab >>Circulating levels of perfluoroalkyl substances and left ventricular geometry of the heart in the elderly.
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2018 (English)In: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 115, p. 295-300Article in journal (Refereed) Published
Abstract [en]

AIMS: Some persistent organic pollutants (POPs) such as hexachlorobenzene (HCB) and some polychlorinated biphenyls (PCBs) have been shown to interfere with myocardial function and geometry. We therefore investigated if also another group of POPs: per- and polyfluoroalkyl substances (PFASs) were associated with alterations in left ventricular geometry.

METHODS: 801 subjects aged 70 years were investigated in a cross-sectional study within the scope of the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. Eight PFASs were detected in >75% of participants´ plasma by ultra-performance liquid chromatograph/tandem mass spectrometry. Left ventricular geometry was determined by echocardiography. Multivariable linear regression was used to investigate the associations between PFASs and left ventricular geometry of the heart after exclusion of subjects with previous myocardial infarction (n = 72).

RESULTS: When adjusting for multiple comparisons, none of the eight PFASs evaluated were significantly related to left ventricular mass. However, perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA) were related to relative wall thickness (RWT) in a negative fashion (p < 0.0021). Besides being inversely related to RWT, PFNA was also positively related to left ventricular end-diastolic volume (LVEDD) (p < 0.0021). These analyses were adjusted for traditional cardiovascular risk factors.

CONCLUSION: In this cross-sectional study, several of the PFASs evaluated, especially PFNA, were related to myocardial geometry: a reduction in relative wall thickness and an increase in left ventricular diameter following adjustment for traditional cardiovascular risk factors, suggesting a role for PFASs in cardiac remodeling.

Keywords
Elderly, Environmental contaminants, Heart, Left ventricular geometry, Per- and polyfluoroalkyl substances (PFASs), Perfluorononanoic acid (PFNA)
National Category
Occupational Health and Environmental Health
Identifiers
urn:nbn:se:uu:diva-348565 (URN)10.1016/j.envint.2018.03.033 (DOI)000432523500032 ()29621717 (PubMedID)
Funder
Swedish Research Council Formas, 2007-2047
Available from: 2018-04-16 Created: 2018-04-16 Last updated: 2018-08-20Bibliographically approved
Nowak, C., Hetty, S., Salihovic, S., Castillejo-Lopez, C., Ganna, A., Cook, N. L., . . . Ingelsson, E. (2018). Glucose challenge metabolomics implicates medium-chain acylcarnitines in insulin resistance. Scientific Reports, 8, Article ID 8691.
Open this publication in new window or tab >>Glucose challenge metabolomics implicates medium-chain acylcarnitines in insulin resistance
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2018 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 8691Article in journal (Refereed) Published
Abstract [en]

Insulin resistance (IR) predisposes to type 2 diabetes and cardiovascular disease but its causes are incompletely understood. Metabolic challenges like the oral glucose tolerance test (OGTT) can reveal pathogenic mechanisms. We aimed to discover associations of IR with metabolite trajectories during OGTT. In 470 non-diabetic men (age 70.6 +/- 0.6 years), plasma samples obtained at 0, 30 and 120 minutes during an OGTT were analyzed by untargeted liquid chromatography-mass spectrometry metabolomics. IR was assessed with the hyperinsulinemic-euglycemic clamp method. We applied age-adjusted linear regression to identify metabolites whose concentration change was related to IR. Nine trajectories, including monounsaturated fatty acids, lysophosphatidylethanolamines and a bile acid, were significantly associated with IR, with the strongest associations observed for medium-chain acylcarnitines C10 and C12, and no associations with L-carnitine or C2-, C8-, C14- or C16-carnitine. Concentrations of C10-and C12-carnitine decreased during OGTT with a blunted decline in participants with worse insulin resistance. Associations persisted after adjustment for obesity, fasting insulin and fasting glucose. In mouse 3T3-L1 adipocytes exposed to different acylcarnitines, we observed blunted insulin-stimulated glucose uptake after treatment with C10-or C12-carnitine. In conclusion, our results identify medium-chain acylcarnitines as possible contributors to IR.

National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-357687 (URN)10.1038/s41598-018-26701-0 (DOI)000434252600004 ()29875472 (PubMedID)
Funder
Knut and Alice Wallenberg Foundation, 2013.0126Swedish Research Council, 2015-03477
Note

Tove Fall and Erik Ingelsson contributed equally to this work.

Available from: 2018-08-23 Created: 2018-08-23 Last updated: 2018-08-23Bibliographically approved
Lind, P. M., Salihovic, S. & Lind, L. (2018). High plasma organochlorine pesticide levels are related to increased biological age as calculated by DNA methylation analysis. Environment International, 113, 109-113
Open this publication in new window or tab >>High plasma organochlorine pesticide levels are related to increased biological age as calculated by DNA methylation analysis
2018 (English)In: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 113, p. 109-113Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Organochlorine pesticides (OCPs) have been shown in the experimental setting to alter DNA methylation. Since DNA methylation changes during the life-span, formulas have been presented to calculate "DNA methylation age" as a measure of biological age.

OBJECTIVES: We aimed to investigate if circulating levels of three OCPs were related to increased DNA methylation age METHODS: 71CpG DNA methylation age (Hannum formula) was calculated based on data from the Illumina 450 k Bead Methylation chip in 1000 subjects in the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS) study (50% women, all aged 70 years at the examination). The difference between DNA methylation age and chronological age was calculated (DiffAge). 2,2-bis (4-chlorophenyl)-1,1-dichloroethene (p,p'-DDE), hexachlorobenzene (HCB), and transnonachlor (TNC) levels were measured in plasma by high-resolution gas chromatography coupled mass spectrometry (HRGC-HRMS).

RESULTS: Increased p,p'-DDE and TNC, but not HCB, levels were related to increased DiffAge both in sex and BMI-adjusted models, as well as in multiple adjusted models (sex, education level, exercise habits, smoking, energy and alcohol consumption and BMI) (p = 0.0051 and p = 0.011, respectively). No significant interactions between the OCPs and sex or BMI regarding DiffAge were found.

CONCLUSION: In this cross-sectional study, increased levels of two out of three OCPs were related to increased DNA methylation age, further suggesting negative health effects in humans of these widespread environmental contaminants.

Place, publisher, year, edition, pages
Elsevier, 2018
Keywords
Biological age, Epidemiology, Methylation, Organochlorine pesticides (OCPs), Transnonachlor, p, p′-DDE
National Category
Occupational Health and Environmental Health
Identifiers
urn:nbn:se:uu:diva-348563 (URN)10.1016/j.envint.2018.01.019 (DOI)000428976700013 ()29421399 (PubMedID)
Funder
Swedish Research Council Formas, 2007-2047 942-2015-756 216-2013-478
Available from: 2018-04-16 Created: 2018-04-16 Last updated: 2018-06-05Bibliographically approved
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