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Liu, C., Marioni, R. E., Hedman, Å. K., Pfeiffer, L., Tsai, P.-C., Reynolds, L. M., . . . Levy, D. (2018). A DNA methylation biomarker of alcohol consumption.. Molecular Psychiatry, 23, 422-433
Open this publication in new window or tab >>A DNA methylation biomarker of alcohol consumption.
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2018 (English)In: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578, Vol. 23, p. 422-433Article in journal (Refereed) Published
Abstract [en]

The lack of reliable measures of alcohol intake is a major obstacle to the diagnosis and treatment of alcohol-related diseases. Epigenetic modifications such as DNA methylation may provide novel biomarkers of alcohol use. To examine this possibility, we performed an epigenome-wide association study of methylation of cytosine-phosphate-guanine dinucleotide (CpG) sites in relation to alcohol intake in 13 population-based cohorts (ntotal=13 317; 54% women; mean age across cohorts 42-76 years) using whole blood (9643 European and 2423 African ancestries) or monocyte-derived DNA (588 European, 263 African and 400 Hispanic ancestry) samples. We performed meta-analysis and variable selection in whole-blood samples of people of European ancestry (n=6926) and identified 144 CpGs that provided substantial discrimination (area under the curve=0.90-0.99) for current heavy alcohol intake (⩾42 g per day in men and ⩾28 g per day in women) in four replication cohorts. The ancestry-stratified meta-analysis in whole blood identified 328 (9643 European ancestry samples) and 165 (2423 African ancestry samples) alcohol-related CpGs at Bonferroni-adjusted P<1 × 10(-7). Analysis of the monocyte-derived DNA (n=1251) identified 62 alcohol-related CpGs at P<1 × 10(-7). In whole-blood samples of people of European ancestry, we detected differential methylation in two neurotransmitter receptor genes, the γ-Aminobutyric acid-A receptor delta and γ-aminobutyric acid B receptor subunit 1; their differential methylation was associated with expression levels of a number of genes involved in immune function. In conclusion, we have identified a robust alcohol-related DNA methylation signature and shown the potential utility of DNA methylation as a clinically useful diagnostic test to detect current heavy alcohol consumption.

National Category
Other Basic Medicine
Identifiers
urn:nbn:se:uu:diva-319698 (URN)10.1038/mp.2016.192 (DOI)000423441700028 ()27843151 (PubMedID)
Note

De tio första författarna delar på förstaförfattarskapet. De sex sista författarna delar på sistaförfattarskapet.

Available from: 2017-04-06 Created: 2017-04-06 Last updated: 2018-03-19Bibliographically approved
Chen, X., Gustafsson, S., Whitington, T., Borne, Y., Lorentzen, E., Sun, J., . . . Magnusson, P. K. E. (2018). A genome-wide association study of IgM antibody against phosphorylcholine: shared genetics and phenotypic relationship to chronic lymphocytic leukemia. Human Molecular Genetics, 27(10), 1809-1818
Open this publication in new window or tab >>A genome-wide association study of IgM antibody against phosphorylcholine: shared genetics and phenotypic relationship to chronic lymphocytic leukemia
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2018 (English)In: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 27, no 10, p. 1809-1818Article in journal (Refereed) Published
Abstract [en]

Phosphorylcholine (PC) is an epitope on oxidized low-density lipoprotein (oxLDL), apoptotic cells and several pathogens like Streptococcus pneumoniae. Immunoglobulin M against PC (IgM anti-PC) has the ability to inhibit uptake of oxLDL by macrophages and increase clearance of apoptotic cells. From our genome-wide association studies (GWASs) in four European-ancestry cohorts, six single nucleotide polymorphisms (SNPs) in 11q24.1 were discovered (in 3002 individuals) and replicated (in 646 individuals) to be associated with serum level of IgM anti-PC (the leading SNP rs35923643-G, combined beta = 0.19, 95% confidence interval 0.13-0.24, P = 4.3 x 10(-11)). The haplotype tagged by rs35923643-G (or its proxy SNP rs735665-A) is also known as the top risk allele for chronic lymphocytic leukemia (CLL), and a main increasing allele for general IgM. By using summary GWAS results of IgM anti-PC and CLL in the polygenic risk score (PRS) analysis, PRS on the basis of IgM anti-PC risk alleles positively associated with CLL risk (explained 0.6% of CLL variance, P = 1.2 x 10(-15)). Functional prediction suggested that rs35923643-G might impede the binding of Runt-related transcription factor 3, a tumor suppressor playing a central role in the immune regulation of cancers. Contrary to the expectations from the shared genetics between IgM anti-PC and CLL, an inverse relationship at the phenotypic level was found in a nested case-control study (30 CLL cases with 90 age-and sex-matched controls), potentially reflecting reverse causation. The suggested function of the top variant as well as the phenotypic association between IgM anti-PC and CLL risk needs replication and motivates further studies.

National Category
Medical Genetics
Identifiers
urn:nbn:se:uu:diva-356866 (URN)10.1093/hmg/ddy094 (DOI)000431886200012 ()29547969 (PubMedID)
Funder
Swedish Research Council, 2017-00641Swedish Heart Lung Foundation, 20070481
Available from: 2018-08-15 Created: 2018-08-15 Last updated: 2018-08-15Bibliographically approved
Jiang, J., Thalamuthu, A., Ho, J. E., Mahajan, A., Ek, W. E., Brown, D. A., . . . Mather, K. A. (2018). A Meta-Analysis of Genome-Wide Association Studies of Growth Differentiation Factor-15 Concentration in Blood. Frontiers in Genetics, 9, Article ID 97.
Open this publication in new window or tab >>A Meta-Analysis of Genome-Wide Association Studies of Growth Differentiation Factor-15 Concentration in Blood
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2018 (English)In: Frontiers in Genetics, ISSN 1664-8021, E-ISSN 1664-8021, Vol. 9, article id 97Article in journal (Refereed) Published
Abstract [en]

Blood levels of growth differentiation factor-15 (GDF-15), also known as macrophage inhibitory cytokine-1 (MIC-1), have been associated with various pathological processes and diseases, including cardiovascular disease and cancer. Prior studies suggest genetic factors play a role in regulating blood MIC-1/GDF-15 concentration. In the current study, we conducted the largest genome-wide association study (GWAS) to date using a sample of similar to 5,400 community-based Caucasian participants, to determine the genetic variants associated with MIC-1/GDF-15 blood concentration. Conditional and joint (COJO), gene-based association, and gene-set enrichment analyses were also carried out to identify novel loci, genes, and pathways. Consistent with prior results, a locus on chromosome 19, which includes nine single nucleotide polymorphisms (SNPs) (top SNP, rs888663, p = 1.690 x 10(-35)), was significantly associated with blood MIC-1/GDF-15 concentration, and explained 21.47% of its variance. COJO analysis showed evidence for two independent signals within this locus. Gene-based analysis confirmed the chromosome 19 locus association and in addition, a putative locus on chromosome 1. Gene-set enrichment analyses showed that the "COPI-mediated anterograde transport" gene-set was associated with MIC-1/GDF15 blood concentration with marginal significance after FDR correction (p = 0.067). In conclusion, a locus on chromosome 19 was associated with MIC-1/GDF-15 blood concentration with genome-wide significance, with evidence for a new locus (chromosome 1). Future studies using independent cohorts are needed to confirm the observed associations especially for the chromosomes 1 locus, and to further investigate and identify the causal SNPs that contribute to MIC-1/GDF-15 levels.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2018
Keywords
genome-wide association study, growth differentiation factor-15, macrophage inhibitory cytokine-1, community-based individuals, chromosome 19
National Category
Medical Genetics
Identifiers
urn:nbn:se:uu:diva-354354 (URN)10.3389/fgene.2018.00097 (DOI)000428198300001 ()
Funder
Knut and Alice Wallenberg FoundationEU, European Research CouncilSwedish Research Council, 2012-1397Swedish Research Council, 2012-1727Swedish Research Council, 2012-2215Swedish Research Council, 80576801Swedish Research Council, 70374401Swedish Foundation for Strategic Research Australian Research Council, DP0774213Australian Research Council, DP0773584Australian Research Council, LP0669645
Available from: 2018-08-08 Created: 2018-08-08 Last updated: 2018-08-08Bibliographically 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
Titova, O. E., Lindberg, E., Elmstahl, S., Lind, L., Schiöth, H. B. & Benedict, C. (2018). Associations Between the Prevalence of Metabolic Syndrome and Sleep Parameters Vary by Age. Frontiers in Endocrinology, 9, Article ID 234.
Open this publication in new window or tab >>Associations Between the Prevalence of Metabolic Syndrome and Sleep Parameters Vary by Age
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2018 (English)In: Frontiers in Endocrinology, ISSN 1664-2392, E-ISSN 1664-2392, Vol. 9, article id 234Article in journal (Refereed) Published
Abstract [en]

Objective: To examine whether the relationship between the metabolic syndrome (MetS) and various sleep parameters [sleep duration, symptoms of sleep-disordered breathing (SDB), and sleep disturbances] varies by age. Methods: Waist circumference, blood pressure, triglycerides, high-density lipoprotein cholesterol, and fasting glucose were used to determine MetS status in a cohort (N = 19,691) of middle-aged (aged 45-64 years) and older (aged >= 65 years) subjects. Habitual sleep duration (short, <= 6 h/day; normal, 7-8 h/day; and long >= 9 h/day), sleep disturbances (such as problems with falling and staying asleep), and symptoms of sleep-disordered breathing (SDB, such as snoring and sleep apneas) were measured by questionnaires. Results: Among the participants, 4,941 subjects (25.1%) fulfilled the criteria for MetS. In the entire sample, both short and long sleep durations were associated with higher prevalence of MetS as compared to normal sleep duration. When stratified by age, a similar pattern was observed for middle-aged subjects (<65 years old; prevalence ratio (PR) [95% CI], 1.13 [1.06-1.22] for short sleep and 1.26 [1.06-1.50] for long sleep duration). In contrast, in older individuals (>= 65 years old), only long sleep duration was linked to a higher prevalence of MetS (1.26 [1.12-1.42]; P < 0.01 for sleep duration x age). In the entire cohort, having at least one SDB symptom >= 4 times per week was linked to an increased prevalence of MetS; however, the PR was higher in middle-aged subjects compared with older subjects (1.50 [1.38-1.63] vs. 1.36 [1.26-1.47], respectively; P < 0.001 for SDB x age). Finally, independent of subjects' age, reports of sleep disturbances (i.e., at least one symptom >= 4 times per week) were associated with a higher likelihood of having MetS (1.12 [1.06-1.18]; P > 0.05 for sleep disturbance x age). Conclusion: Our results suggest that age may modify the associations between some sleep parameters and the prevalence of MetS.

Keywords
sleep duration, sleep disturbance, sleep-disordered breathing, metabolic syndrome, age
National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:uu:diva-356873 (URN)10.3389/fendo.2018.00234 (DOI)000431867800001 ()29867766 (PubMedID)
Funder
Swedish Research Council, 2015-03100The Swedish Brain FoundationNovo Nordisk, NNF14OC0009349
Available from: 2018-08-09 Created: 2018-08-09 Last updated: 2018-08-09Bibliographically 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
Cai, G.-H., Janson, C., Theorell-Haglöw, J., Benedict, C., Elmståhl, S., Lind, L. & Lindberg, E. (2018). Both Weight at Age 20 and Weight Gain Have an Impact on Sleep Disturbances Later in Life: Results of the EpiHealth Study. Sleep, 41(1), Article ID zsx176.
Open this publication in new window or tab >>Both Weight at Age 20 and Weight Gain Have an Impact on Sleep Disturbances Later in Life: Results of the EpiHealth Study
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2018 (English)In: Sleep, ISSN 0161-8105, E-ISSN 1550-9109, Vol. 41, no 1, article id zsx176Article in journal (Refereed) Published
Abstract [en]

Study Objectives: Obesity is often associated with impaired sleep, whereas the impact of body mass index (BMI) at younger age and previous weight gain on sleep problems remains unknown.

Methods: The present study utilized data from the Swedish EpiHealth cohort study. A total of 15 845 participants (45-75 years) filled out an internet-based questionnaire. BMI was calculated from both measured data at study time and self-reported data at age 20 from the questionnaire.

Results: Sleep-related symptoms were most common among obese individuals (BMI >30 kg/m(2)). An association between weight gain and sleep problems was found and those with a low BMI at age 20 were most vulnerable to weight gain when it came to risk of sleep problems. Among those who were underweight (BMI <18.5 kg/m(2)) at age 20, weight gain (kg/year) was associated with difficulties initiating sleep with an adjusted OR of 2.64 (95% CI: 1.51-4.62) after adjusting for age, sex, smoking, alcohol consumption, physical activity, education, and civil status. The corresponding adjusted OR's among those who had been normal weight (BMI 18.5-24.99) and overweight (BMI 25-29.99 kg/m(2)) at age 20 were 1.89 (1.47-2.45) and 1.02 (0.48-2.13), respectively. Also difficulties maintaining sleep and snoring were most strongly related to weight gain among those who were underweight at age 20 with decreasing odds with increasing BMI at that age.

Conclusions: Sleep problems are related to weight gain and obesity. The impact of weight is most pronounced among those who had a low BMI when young.

Place, publisher, year, edition, pages
OXFORD UNIV PRESS INC, 2018
Keywords
epidemiology, insomnia, obesity, aging, weight gain, EpiHealth study, body mass index (BMI), Epworth Sleepiness Scale (ESS), sleep problems, snoring
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-342460 (URN)10.1093/sleep/zsx176 (DOI)000422879100012 ()
Funder
Swedish Research Council
Available from: 2018-02-26 Created: 2018-02-26 Last updated: 2018-02-26Bibliographically 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
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0003-2335-8542

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