| 1. |
- Ramdas, S., et al.
(author)
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A multi-layer functional genomic analysis to understand noncoding genetic variation in lipids
- 2022
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In: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 109:8, s. 1366-1387
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Journal article (peer-reviewed)abstract
- A major challenge of genome-wide association studies (GWASs) is to translate phenotypic associations into biological insights. Here, we integrate a large GWAS on blood lipids involving 1.6 million individuals from five ancestries with a wide array of functional genomic datasets to discover regulatory mechanisms underlying lipid associations. We first prioritize lipid-associated genes with expression quantitative trait locus (eQTL) colocalizations and then add chromatin interaction data to narrow the search for functional genes. Polygenic enrichment analysis across 697 annotations from a host of tissues and cell types confirms the central role of the liver in lipid levels and highlights the selective enrichment of adipose-specific chromatin marks in high-density lipoprotein cholesterol and triglycerides. Overlapping transcription factor (TF) binding sites with lipid-associated loci identifies TFs relevant in lipid biology. In addition, we present an integrative framework to prioritize causal variants at GWAS loci, producing a comprehensive list of candidate causal genes and variants with multiple layers of functional evidence. We highlight two of the prioritized genes, CREBRF and RRBP1, which show convergent evidence across functional datasets supporting their roles in lipid biology.
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| 2. |
- Justice, A. E., et al.
(author)
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Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits
- 2017
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Journal article (peer-reviewed)abstract
- Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution.
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| 3. |
- Turcot, Valerie, et al.
(author)
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Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity
- 2018
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In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:1, s. 26-41
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Journal article (peer-reviewed)abstract
- Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are similar to 10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed similar to 7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.
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| 4. |
- Kanoni, Stavroula, et al.
(author)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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In: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Journal article (peer-reviewed)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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| 5. |
- Marouli, Eirini, et al.
(author)
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Rare and low-frequency coding variants alter human adult height
- 2017
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 542:7640, s. 186-190
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Journal article (peer-reviewed)abstract
- Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.
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| 6. |
- Mahajan, Anubha, et al.
(author)
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Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation
- 2022
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In: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 54:5, s. 560-572
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Journal article (peer-reviewed)abstract
- We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 x 10(-9)), which were delineated to 338 distinct association signals. Fine-mapping of these signals was enhanced by the increased sample size and expanded population diversity of the multi-ancestry meta-analysis, which localized 54.4% of T2D associations to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying the foundations for functional investigations. Multi-ancestry genetic risk scores enhanced transferability of T2D prediction across diverse populations. Our study provides a step toward more effective clinical translation of T2D GWAS to improve global health for all, irrespective of genetic background. Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.
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| 7. |
- Lakens, Daniel, et al.
(author)
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Justify your alpha
- 2018
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In: Nature Human Behaviour. - : Nature Publishing Group. - 2397-3374. ; 2:3, s. 168-171
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Journal article (peer-reviewed)abstract
- In response to recommendations to redefine statistical significance to P ≤ 0.005, we propose that researchers should transparently report and justify all choices they make when designing a study, including the alpha level.
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| 8. |
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| 9. |
- Bauer, Michael, et al.
(author)
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Association between solar insolation and a history of suicide attempts in bipolar I disorder.
- 2019
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In: Journal of psychiatric research. - : Elsevier BV. - 1879-1379 .- 0022-3956. ; 113, s. 1-9
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Journal article (peer-reviewed)abstract
- In many international studies, rates of completed suicide and suicide attempts have a seasonal pattern that peaks in spring or summer. This exploratory study investigated the association between solar insolation and a history of suicide attempt in patients with bipolar I disorder. Solar insolation is the amount of electromagnetic energy from the Sun striking a surface area on Earth. Data were collected previously from 5536 patients with bipolar I disorder at 50 collection sites in 32 countries at a wide range of latitudes in both hemispheres. Suicide related data were available for 3365 patients from 310 onset locations in 51 countries. 1047 (31.1%) had a history of suicide attempt. There was a significant inverse association between a history of suicide attempt and the ratio of mean winter solar insolation/mean summer solar insolation. This ratio is smallest near the poles where the winter insolation is very small compared to the summer insolation. This ratio is largest near the equator where there is relatively little variation in the insolation over the year. Other variables in the model that were positively associated with suicide attempt were being female, a history of alcohol or substance abuse, and being in a younger birth cohort. Living in a country with a state-sponsored religion decreased the association. (All estimated coefficients p<0.01). In summary, living in locations with large changes in solar insolation between winter and summer may be associated with increased suicide attempts in patients with bipolar disorder. Further investigation of the impacts of solar insolation on the course of bipolar disorder is needed.
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| 10. |
- Hreinsdottir, S., et al.
(author)
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Volcanic plume height correlated with magma-pressure change at Grimsvotn Volcano, Iceland
- 2014
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In: Nature Geoscience. - : Springer Science and Business Media LLC. - 1752-0894 .- 1752-0908. ; 7:3, s. 214-218
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Journal article (peer-reviewed)abstract
- Magma flow during volcanic eruptions causes surface deformation that can be used to constrain the location, geometry and internal pressure evolution of the underlying magmatic source(1). The height of the volcanic plumes during explosive eruptions also varies with magma flow rate, in a nonlinear way(2,3). In May 2011, an explosive eruption at Grimsvotn Volcano, Iceland, erupted about 0.27 km(3) dense-rock equivalent of basaltic magma in an eruption plume that was about 20 km high. Here we use Global Positioning System (GPS) and tilt data, measured before and during the eruption at Grimsvotn Volcano, to show that the rate of pressure change in an underlying magma chamber correlates with the height of the volcanic plume over the course of the eruption. We interpret ground deformation of the volcano, measured by geodesy, to result from a pressure drop within a magma chamber at about 1.7 km depth. We estimate the rate of magma discharge and the associated evolution of the plume height by differentiating the co-eruptive pressure drop with time. The time from the initiation of the pressure drop to the onset of the eruption was about 60 min, with about 25% of the total pressure change preceding the eruption. Near-real-time geodetic observations can thus be useful for both timely eruption warnings and for constraining the evolution of volcanic plumes.
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| 11. |
- Abolfathi, Bela, et al.
(author)
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The LSST DESC DC2 Simulated Sky Survey
- 2021
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In: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 253:31
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Journal article (peer-reviewed)abstract
- We describe the simulated sky survey underlying the second data challenge (DC2) carried out in preparation for analysis of the Vera C. Rubin Observatory Legacy Survey of Space and Time (LSST) by the LSST Dark Energy Science Collaboration (LSST DESC). Significant connections across multiple science domains will be a hallmark of LSST; the DC2 program represents a unique modeling effort that stresses this interconnectivity in a way that has not been attempted before. This effort encompasses a full end-to-end approach: starting from a large N-body simulation, through setting up LSST-like observations including realistic cadences, through image simulations, and finally processing with Rubin's LSST Science Pipelines. This last step ensures that we generate data products resembling those to be delivered by the Rubin Observatory as closely as is currently possible. The simulated DC2 sky survey covers six optical bands in a wide-fast-deep area of approximately 300 deg2, as well as a deep drilling field of approximately 1 deg2. We simulate 5 yr of the planned 10 yr survey. The DC2 sky survey has multiple purposes. First, the LSST DESC working groups can use the data set to develop a range of DESC analysis pipelines to prepare for the advent of actual data. Second, it serves as a realistic test bed for the image processing software under development for LSST by the Rubin Observatory. In particular, simulated data provide a controlled way to investigate certain image-level systematic effects. Finally, the DC2 sky survey enables the exploration of new scientific ideas in both static and time domain cosmology.
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| 12. |
- Adamo, A., et al.
(author)
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Revealing a ring-like cluster complex in a tidal tail of the starburst galaxy NGC 2146
- 2012
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In: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 426:2, s. 1185-1194
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Journal article (peer-reviewed)abstract
- We report the discovery of a ring-like cluster complex in the starburst galaxy NGC?2146. The Ruby Ring, so named due to its appearance, shows a clear ring-like distribution of star clusters around a central object. It is located in one of the tidal streams that surround the galaxy. NGC?2146 is part of the Snapshot Hubble U-band Cluster Survey (SHUCS). The WFC3/F336W data have added critical information to the available archival Hubble Space Telescope imaging set of NGC?2146, allowing us to determine ages, masses and extinctions of the clusters in the Ruby Ring. These properties have then been used to investigate the formation of this extraordinary system. We find evidence of a spatial and temporal correlation between the central cluster and the clusters in the ring. The latter are about 4?Myr younger than the central cluster, which has an age of 7?Myr. This result is supported by the Ha emission which is strongly coincident with the ring, and weaker at the position of the central cluster. From the derived total Ha luminosity of the system, we constrain the star formation rate density to be quite high (SSFR = 0.47?M??yr-1?kpc-2). The Ruby Ring is the product of an intense and localized burst of star formation, similar to the extended cluster complexes observed in M?51 and the Antennae, but more impressive because it is quite isolated. The central cluster contains only 5 per cent of the total stellar mass in the clusters that are determined within the complex. The ring-like morphology, the age spread and the mass ratio support a triggering formation scenario for this complex. We discuss the formation of the Ruby Ring in a collect and collapse framework. The predictions made by this model agree quite well with the estimated bubble radius and expansion velocity produced by the feedback from the central cluster, making the Ruby Ring an interesting case of triggered star formation.
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| 13. |
- Barillot, T., et al.
(author)
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Correlation-Driven Transient Hole Dynamics Resolved in Space and Time in the Isopropanol Molecule
- 2021
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In: Physical Review X. - : American Physical Society. - 2160-3308. ; 11:3
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Journal article (peer-reviewed)abstract
- The possibility of suddenly ionized molecules undergoing extremely fast electron hole (or hole) dynamics prior to significant structural change was first recognized more than 20 years ago and termed charge migration. The accurate probing of ultrafast electron hole dynamics requires measurements that have both sufficient temporal resolution and can detect the localization of a specific hole within the molecule. We report an investigation of the dynamics of inner valence hole states in isopropanol where we use an x-ray pump-x-ray probe experiment, with site and state-specific probing of a transient hole state localized near the oxygen atom in the molecule, together with an ab initio theoretical treatment. We record the signature of transient hole dynamics and make the first tentative observation of dynamics driven by frustrated Auger-Meitner transitions. We verify that the effective hole lifetime is consistent with our theoretical prediction. This state-specific measurement paves the way to widespread application for observations of transient hole dynamics localized in space and time in molecules and thus to charge transfer phenomena that are fundamental in chemical and material physics.
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| 14. |
- Bastian, N., et al.
(author)
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Evidence for environmentally dependent cluster disruption in M83
- 2011
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In: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966 .- 1745-3925. ; 417:1, s. l6-L10
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Journal article (peer-reviewed)abstract
- Using multiwavelength imaging from the Wide Field Camera 3 on the Hubble Space Telescope we study the stellar cluster populations of two adjacent fields in the nearby face-on spiral galaxy, M83. The observations cover the galactic centre and reach out to similar to 6 kpc, thereby spanning a large range of environmental conditions, ideal for testing empirical laws of cluster disruption. The clusters are selected by visual inspection to be centrally concentrated, symmetric and resolved on the images. We find that a large fraction of objects detected by automated algorithms (e. g. SEXTRACTOR or DAOFIND) are not clusters, but rather are associations. These are likely to disperse into the field on time-scales of tens of Myr due to their lower stellar densities and not due to gas expulsion (i.e. they were never gravitationally bound). We split the sample into two discrete fields (inner and outer regions of the galaxy) and search for evidence of environmentally dependent cluster disruption. Colour-colour diagrams of the clusters, when compared to simple stellar population models, already indicate that a much larger fraction of the clusters in the outer field are older by tens of Myr than in the inner field. This impression is quantified by estimating each cluster's properties (age, mass and extinction) and comparing the age/mass distributions between the two fields. Our results are inconsistent with 'universal' age and mass distributions of clusters, and instead show that the ambient environment strongly affects the observed populations.
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| 15. |
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| 16. |
- Graham, Ian, et al.
(author)
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European guidelines on cardiovascular disease prevention in clinical practice: full text. Fourth Joint Task Force of the European Society of Cardiology and other societies on cardiovascular disease prevention in clinical practice (constituted by representatives of nine societies and by invited experts).
- 2007
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In: European journal of cardiovascular prevention and rehabilitation : official journal of the European Society of Cardiology, Working Groups on Epidemiology & Prevention and Cardiac Rehabilitation and Exercise Physiology. - : Oxford University Press (OUP). - 1741-8267. ; 14 Suppl 2
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Journal article (peer-reviewed)abstract
- Other experts who contributed to parts of the guidelines: Edmond Walma, Tony Fitzgerald, Marie Therese Cooney, Alexandra Dudina European Society of Cardiology (ESC) Committee for Practice Guidelines (CPG): Alec Vahanian (Chairperson), John Camm, Raffaele De Caterina, Veronica Dean, Kenneth Dickstein, Christian Funck-Brentano, Gerasimos Filippatos, Irene Hellemans, Steen Dalby Kristensen, Keith McGregor, Udo Sechtem, Sigmund Silber, Michal Tendera, Petr Widimsky, Jose Luis Zamorano Document reviewers: Irene Hellemans (CPG Review Co-ordinator), Attila Altiner, Enzo Bonora, Paul N. Durrington, Robert Fagard, Simona Giampaoli, Harry Hemingway, Jan Hakansson, Sverre Erik Kjeldsen, Mogens Lytken Larsen, Giuseppe Mancia, Athanasios J. Manolis, Kristina Orth-Gomer, Terje Pedersen, Mike Rayner, Lars Ryden, Mario Sammut, Neil Schneiderman, Anton F. Stalenhoef, Lale Tokgözoglu, Olov Wiklund, Antonis Zampelas
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| 17. |
- Horner, Nolan S, et al.
(author)
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Timing of hip hemiarthroplasty and the influence on prosthetic joint infection.
- 2020
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In: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 15:3
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Journal article (peer-reviewed)abstract
- Previous research suggested that patients have increased risk of infection with increased time from presentation with a femoral neck fracture to treatment with a hip hemiarthroplasty (HHA). The purpose of this study was to determine if rates of prosthetic joint infections within 3 months of surgery was affected by the time from patient presentation with a femoral neck fracture to the time of treatment with HHA.Acute hip fractures treated with HHA between 2005 and 2017 at three centres in Norway were enrolled in the study. Multi-trauma patients were excluded. Univariable analysis was performed to determine any significant effect of pre-operative waiting time on infection rate. Two pre-planned analyses dichotomizing pre-operative waiting time cut-offs were performed.There were 2300 patients with an average age of 82 (range, 48-100) years included of which 3.4% experienced a prosthetic joint infection within 3 months. The primary analysis found no significant difference in infection rate depending on time to surgery (OR = 1.06 (95% CI 0.94-1.20, p = 0.33)). The secondary analyses showed no significant differences in infection rates when comparing pre-operative waiting time of <24 hours vs ≥24 hours (OR = 0.92 (95% CI 0.58-1.46, p = 0.73)) and <48 hours vs ≥48 hours (OR = 1.39 (95% CI 0.81-2.38, p = 0.23)).Based off of a large retrospective Norwegian database of hip fractures there did not appear to be a significant difference in infection rate based on pre-operative wait time to surgery.
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| 18. |
- Konstantopoulos, I. S., et al.
(author)
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THE SNAPSHOT HUBBLE U-BAND CLUSTER SURVEY (SHUCS). I. SURVEY DESCRIPTION AND FIRST APPLICATION TO THE MIXED STAR CLUSTER POPULATION OF NGC 4041
- 2013
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In: Astronomical Journal. - : American Astronomical Society. - 0004-6256 .- 1538-3881. ; 145:5, s. 137-
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Journal article (peer-reviewed)abstract
- We present the Snapshot Hubble U-band Cluster Survey (SHUCS), a project aimed at characterizing the star cluster populations of 10 nearby galaxies (d < 23 Mpc, half within approximate to 12 Mpc) through new F336W (U-band equivalent) imaging from Wide Field Camera 3, and archival BVI-equivalent data with the Hubble Space Telescope. Completing the UBVI baseline reduces the age-extinction degeneracy of optical colors, thus enabling the measurement of reliable ages and masses for the thousands of clusters covered by our survey. The sample consists chiefly of face-on spiral galaxies at low inclination, in various degrees of isolation (isolated, in group, merging), and includes two active galactic nucleus hosts. This first paper outlines the survey itself, the observational datasets, the analysis methods, and presents a proof-of-concept study of the large-scale properties and star cluster population of NGC 4041, a massive SAbc galaxy at a distance of approximate to 23 Mpc, and part of a small grouping of six giant members. We resolve two structural components with distinct stellar populations, a morphology more akin to merging and interacting systems. We also find strong evidence of a truncated, Schechter-type mass function, and a similarly segmented luminosity function. These results indicate that binning must erase much of the substructure present in the mass and luminosity functions, and might account for the conflicting reports on the intrinsic shape of these functions in the literature. We also note a tidal feature in the outskirts of the galaxy in Galaxy Evolution Explorer UV imaging, and follow it up with a comprehensive multi-wavelength study of NGC 4041 and its parent group. We deduce a minor merger as a likely cause of its segmented structure and the observed pattern of a radially decreasing star formation rate. We propose that combining the study of star cluster populations with broadband metrics is not only advantageous, but often easily achievable thorough archival datasets.
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| 19. |
- Mapelli, Valeria, 1978, et al.
(author)
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The interplay between sulphur and selenium metabolism in yeast influences the intracellular redox balance
- 2012
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In: FEMS Yeast Research. - : Oxford University Press (OUP). - 1567-1356 .- 1567-1364. ; 12:1, s. 20-32
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Journal article (peer-reviewed)abstract
- Selenium is an essential element for most eukaryotic organisms, including humans. The balance between Se toxicity and its beneficial effects is very delicate. It has been demonstrated that a diet enriched of Se has cancer prevention potential in humans. The most popular commercial Se supplementation is selenized yeast, which is produced in a fermentation process using an inorganic source of Se. Here we show that uptake of Se, Se toxic effects and intracellular Se-metabolite profile are largely influenced by the level of sulphur source supplied during the fermentation. A Yap1-dependent oxidative stress response is active when yeast actively metabolizes Se and this response is linked to the generation of an intracellular redox imbalance. The redox imbalance derives from a disproportionate ratio between the reduced and oxidized form of glutathione and also from the influence of Se metabolism on the central carbon metabolism. The observed increase of glycerol production rate concomitant with the inhibition of ethanol formation in the presence of Se can be ascribed to the occurrence of redox imbalance that triggers glycerol biosynthesis to replenish the pool of NAD+.
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| 20. |
- Ravn-Haren, Gitte, et al.
(author)
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A short-term intervention trial with selenate, selenium-enriched yeast and selenium-enriched milk: effects on oxidative defence regulation
- 2008
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In: British Journal of Nutrition. - 1475-2662. ; 99:4, s. 883-892
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Journal article (peer-reviewed)abstract
- Increased Se intakes have been associated with decreased risk of cancer and CVD. Several mechanisms have been proposed, including antioxidant effects through selenoproteins, induction of carcinogen metabolism and effects on the blood lipid profile. In a 4 x 1 week randomised, double-blind cross-over study, healthy young men supplemented their usual diet with selenate, Se-enriched yeast, Se-enriched milk or placebo (Se dose was 300 mu g/d for selenate and Se-enriched yeast, and about 480 mu g/d for Se-enriched milk) followed by 8-week washout periods. All Se sources increased serum Se levels after supplementation for 1 week. The effect of the organic forms did not differ significantly and both increased serum Se more than selenate. Conversely, thrombocyte glutathione peroxidase (GPX) was increased in the periods where subjects were supplemented with selenate but not in those where they were given Se-enriched yeast or Se-enriched milk. We found no effect on plasma lipid resistance to oxidation, total cholesterol, TAG, HDL- and LDL-cholesterol, GPX, glutathione reductase (GR) and glutathione S-transferase (GST) activities measured in erythrocytes, GPX and GR activities determined in plasma, or GR and GST activities in thrombocytes. Leucocyte expression of genes encoding selenoproteins (GPX1, TrR1 and SelP), and of electrophile response element-regulated genes (GCLC, Fra1 and NQO1) were likewise unaffected at all time points following intervention. We conclude that thrombocyte GPX is specifically increased by short-term selenate supplementation, but not by short-term supplementation with organic Se. Short-term Se supplementation does not seem to affect blood lipid markers or expression and activity of selected enzymes and a transcription factor involved in glutathione-mediated detoxification and antioxidation.
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