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Sökning: WFRF:(Drevon Christian A.)

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  • Delgado-Lista, Javier, et al. (författare)
  • Top Single Nucleotide Polymorphisms Affecting Carbohydrate Metabolism in Metabolic Syndrome : From the LIPGENE Study
  • 2014
  • Ingår i: Journal of Clinical Endocrinology and Metabolism. - 0021-972X .- 1945-7197. ; 99:2, s. E384-E389
  • Tidskriftsartikel (refereegranskat)abstract
    • Rationale: Metabolic syndrome (MetS) is a high-prevalence condition characterized by altered energy metabolism, insulin resistance, and elevated cardiovascular risk. Objectives: Although many individual single nucleotide polymorphisms (SNPs) have been linked to certain MetS features, there are few studies analyzing the influence of SNPs on carbohydrate metabolism in MetS. Methods: A total of 904 SNPs (tag SNPs and functional SNPs) were tested for influence on 8 fasting and dynamic markers of carbohydrate metabolism, by performance of an intravenous glucose tolerance test in 450 participants in the LIPGENE study. Findings: From 382 initial gene-phenotype associations between SNPs and any phenotypic variables, 61 (16% of the preselected variables) remained significant after bootstrapping. Top SNPs affecting glucose metabolism variables were as follows: fasting glucose, rs26125 (PPARGC1B); fasting insulin, rs4759277 (LRP1); C-peptide, rs4759277 (LRP1); homeostasis assessment of insulin resistance, rs4759277 (LRP1); quantitative insulin sensitivity check index, rs184003 (AGER); sensitivity index, rs7301876 (ABCC9), acute insulin response to glucose, rs290481 (TCF7L2); and disposition index, rs12691 (CEBPA). Conclusions: We describe here the top SNPs linked to phenotypic features in carbohydrate metabolism among approximately 1000 candidate gene variations in fasting and postprandial samples of 450 patients with MetS from the LIPGENE study.
  • Garcia-Rios, Antonio, et al. (författare)
  • A Period 2 Genetic Variant Interacts with Plasma SFA to Modify Plasma Lipid Concentrations in Adults with Metabolic Syndrome
  • 2012
  • Ingår i: Journal of Nutrition. - 0022-3166 .- 1541-6100. ; 142:7, s. 1213-1218
  • Tidskriftsartikel (refereegranskat)abstract
    • Genetic variants of Period 2 (PER2), a circadian clock gene, have been linked to metabolic syndrome (MetS). However, it is still unknown whether these genetic variants interact with the various types of plasma fatty acids. This study investigated whether common single nucleotide polymorphisms (SNPs) in the PER2 locus (rs934945 and rs2304672) interact with various classes of plasma fatty acids to modulate plasma lipid metabolism in 381 participants with MetS in the European LIPGENE study. Interestingly, the rs2304672 SNP interacted with plasma total SFA concentrations to affect fasting plasma TG, TG-rich lipoprotein (TRL-TG), total cholesterol, apoC-II, apoB, and apoB-48 concentrations (P-interaction <0.001-0.046). Carriers of the minor allele (GC+GG) with the highest SFA concentration (>median) had a higher plasma TG concentration (P = 0.001) and higher TRL-TG (P < 0.001) than the CC genotype. In addition, participants carrying the minor G allele for rs2304672 SNP and with a higher SFA concentration (>median) had higher plasma concentrations of apo C-II (P < 0.001), apo C-III (P = 0.009), and apoB-48 (P = 0.028) compared with the homozygotes for the major allele (CC). In summary, the rs2304672 polymorphism in the PER2 gene locus may influence lipid metabolism by interacting with the plasma total SEA concentration in participants with MetS. The understanding of these gene-nutrient interactions could help to provide a better knowledge of the pathogenesis in MetS. 
  • Nyberg, Lars, 1966-, et al. (författare)
  • Individual differences in brain aging : heterogeneity in cortico-hippocampal but not caudate atrophy rates
  • 2022
  • Ingår i: Cerebral Cortex. - 1047-3211 .- 1460-2199.
  • Tidskriftsartikel (refereegranskat)abstract
    • It is well documented that some brain regions, such as association cortices, caudate, and hippocampus, are particularly prone to age-related atrophy, but it has been hypothesized that there are individual differences in atrophy profiles. Here, we document heterogeneity in regional-atrophy patterns using latent-profile analysis of 1,482 longitudinal magnetic resonance imaging observations. The results supported a 2-group solution reflecting differences in atrophy rates in cortical regions and hippocampus along with comparable caudate atrophy. The higher-atrophy group had the most marked atrophy in hippocampus and also lower episodic memory, and their normal caudate atrophy rate was accompanied by larger baseline volumes. Our findings support and refine models of heterogeneity in brain aging and suggest distinct mechanisms of atrophy in striatal versus hippocampal-cortical systems.
  • Paniagua, J. A., et al. (författare)
  • A low-fat high-carbohydrate diet supplemented with long-chain n-3 PUFA reduces the risk of the metabolic syndrome
  • 2011
  • Ingår i: Atherosclerosis. - 0021-9150 .- 1879-1484. ; 218:2, s. 443-450
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Dietary changes are major factor in determining cardiovascular risk. We assessed the effects of isoenergetic diets with different fat quantity and quality on the incidence and regression of the metabolic syndrome (MetS) from the LIPGENE project. Methods and design: Clinical intervention study: the patients (n = 337) were randomly assigned to one of four diets for 12 weeks each: two high fat diets, one rich in saturated fat (HSFA) and the other rich in monounsaturated fat (HMUFA), and two low fat diets, one high in complex carbohydrates (LFHCC) supplemented with 1.24 g/day of long-chain n-3 polyunsaturated fatty acids (LFHCC n-3) and the other LFHCC diet with placebo (LFHCC). Measurements: the effects on MetS risk criteria were recorded before and after the intervention period. Results: An enlarged waist circumference (>= 88 cm for women and >= 102 cm for men) was present among 95% of the participants, 88% had elevated blood pressure (>130/85 mm Hg or antihypertensive drugs), 77% had elevated fasting plasma glucose (>= 5.55 mmol/L), 51% were hypertriacylglycerolemic (>= 1.7 mmol/L), and 72% had low HDL cholesterol (<1.0 mmol/L for men, and <1.3 mmol/L for women). The prevalence of enlarged waist circumference, hypertension and hypertriacylglycerolemia were reduced after the LFHCC n-3 diet (p<0.05). Thus the prevalence of MetS fell by 20.5% after LFHCC n-3 diet compared with the HSFA (10.6%), HMUFA (12%) diet or LFHCC (10.4%) diets (p<0.028). Conclusions: The consumption of a low-fat high-carbohydrate supplemented with n-3 diet reduced the risk of MetS as compared with isoenergetic high-fat (HSFA and HMUFA) and LFHCC diets. 
  • Petersson, Helena, et al. (författare)
  • Effects of dietary fat modification on oxidative stress and inflammatory markers in the LIPGENE study
  • 2010
  • Ingår i: British Journal of Nutrition. - 0007-1145 .- 1475-2662. ; 104:9, s. 1357-1362
  • Tidskriftsartikel (refereegranskat)abstract
    • Subjects with the metabolic syndrome (MetS) have enhanced oxidative stress and inflammation. Dietary fat quality has been proposed to be implicated in these conditions. We investigated the impact of four diets distinct in fat quantity and quality on 8-iso-PGF2α (a major F2-isoprostane and oxidative stress indicator), 15-keto-13,14-dihydro-PGF2α (15-keto-dihydro-PGF2α, a major PGF2α metabolite and marker of cyclooxygenase-mediated inflammation) and C-reactive protein (CRP). In a 12-week parallel multicentre dietary intervention study (LIPGENE), 417 volunteers with the MetS were randomly assigned to one of the four diets: two high-fat diets (38 % energy (%E)) rich in SFA or MUFA and two low-fat high-complex carbohydrate diets (28 %E) with (LFHCC n-3) or without (LFHCC) 1·24 g/d of very long chain n-3 fatty acid supplementation. Urinary levels of 8-iso-PGF2α and 15-keto-dihydro-PGF2α were determined by RIA and adjusted for urinary creatinine levels. Serum concentration of CRP was measured by ELISA. Neither concentrations of 8-iso-PGF2α and 15-keto-dihydro-PGF2α nor those of CRP differed between diet groups at baseline (P>0·07) or at the end of the study (P>0·44). Also, no differences in changes of the markers were observed between the diet groups (8-iso-PGF2α, P = 0·83; 15-keto-dihydro-PGF2α, P = 0·45; and CRP, P = 0·97). In conclusion, a 12-week dietary fat modification did not affect the investigated markers of oxidative stress and inflammation among subjects with the MetS in the LIPGENE study.
  • Walsh, Marianne C., et al. (författare)
  • Impact of geographical region on urinary metabolomic and plasma fatty acid profiles in subjects with the metabolic syndrome across Europe : the LIPGENE study
  • 2014
  • Ingår i: British Journal of Nutrition. - 0007-1145 .- 1475-2662. ; 111:3, s. 424-431
  • Tidskriftsartikel (refereegranskat)abstract
    • The application of metabolomics in multi-centre studies is increasing. The aim of the present study was to assess the effects of geographical location on the metabolic profiles of individuals with the metabolic syndrome. Blood and urine samples were collected from 219 adults from seven European centres participating in the LIPGENE project (Diet, genomics and the metabolic syndrome: an integrated nutrition, agro-food, social and economic analysis). Nutrient intakes, BMI, waist:hip ratio, blood pressure, and plasma glucose, insulin and blood lipid levels were assessed. Plasma fatty acid levels and urine were assessed using a metabolomic technique. The separation of three European geographical groups (NW, northwest; NE, northeast; SW, southwest) was identified using partial least-squares discriminant analysis models for urine ((RX)-X-2: 0.33, Q(2): 0.39) and plasma fatty acid ((RX)-X-2: 032, Q(2): 0.60) data. The NW group was characterised by higher levels of urinary hippurate and N-methylnicotinate. The NE group was characterised by higher levels of urinary creatine and citrate and plasma EPA (20:5 n-3). The SW group was characterised by higher levels of urinary trimethylamine oxide and lower levels of plasma EPA. The indicators of metabolic health appeared to be consistent across the groups. The SW group had higher intakes of total fat and MUFA compared with both the NW and NE groups (P <= 0.001). The NE group had higher intakes of fibre and n-3 and n-6 fatty acids compared with both the NW and SW groups (all P<0.001). It is likely that differences in dietary intakes contributed to the separation of the three groups. Evaluation of geographical factors including diet should be considered in the interpretation of metabolomic data from multi-centre studies.
  • Fallaize, Rosalind, et al. (författare)
  • APOE genotype influences insulin resistance, apolipoprotein CII and CIII according to plasma fatty acid profile in the Metabolic Syndrome
  • 2017
  • Ingår i: Scientific Reports. - 2045-2322. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • Metabolic markers associated with the Metabolic Syndrome (MetS) may be affected by interactions between the APOE genotype and plasma fatty acids (FA). In this study, we explored FA-gene interactions between the missense APOE polymorphisms and FA status on metabolic markers in MetS. Plasma FA, blood pressure, insulin sensitivity and lipid concentrations were determined at baseline and following a 12-week randomized, controlled, parallel, dietary FA intervention in 442 adults with MetS (LIPGENE study). FA-APOE gene interactions at baseline and following change in plasma FA were assessed using adjusted general linear models. At baseline E4 carriers had higher plasma concentrations of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (apo B) compared with E2 carriers; and higher TC, LDL-C and apo B compared with E3/E3. Whilst elevated plasma n-3 polyunsaturated FA (PUFA) was associated with a beneficially lower concentration of apo CIII in E2 carriers, a high proportion of plasma C16:0 was associated with insulin resistance in E4 carriers. Following FA intervention, a reduction in plasma long-chain n-3 PUFA was associated with a reduction in apo CII concentration in E2 carriers. Our novel data suggest that individuals with MetS may benefit from personalized dietary interventions based on APOE genotype.
  • Ferguson, Jane F, et al. (författare)
  • Gene-nutrient interactions in the metabolic syndrome : single nucleotide polymorphisms in ADIPOQ and ADIPOR1 interact with plasma saturated fatty acids to modulate insulin resistance
  • 2010
  • Ingår i: American Journal of Clinical Nutrition. - 0002-9165 .- 1938-3207. ; 91:3, s. 794-801
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Progression of the metabolic syndrome (MetS) is determined by genetic and environmental factors. Gene-environment interactions may be important in modulating the susceptibility to the development of MetS traits. OBJECTIVE: Gene-nutrient interactions were examined in MetS subjects to determine interactions between single nucleotide polymorphisms (SNPs) in the adiponectin gene (ADIPOQ) and its receptors (ADIPOR1 and ADIPOR2) and plasma fatty acid composition and their effects on MetS characteristics. DESIGN: Plasma fatty acid composition, insulin sensitivity, plasma adiponectin and lipid concentrations, and ADIPOQ, ADIPOR1, and ADIPOR2 SNP genotypes were determined in a cross-sectional analysis of 451 subjects with the MetS who participated in the LIPGENE (Diet, Genomics, and the Metabolic Syndrome: an Integrated Nutrition, Agro-food, Social, and Economic Analysis) dietary intervention study and were repeated in 1754 subjects from the LIPGENE-SU.VI.MAX (SUpplementation en VItamines et Minéraux AntioXydants) case-control study (http://www.ucd.ie/lipgene). RESULTS: Single SNP effects were detected in the cohort. Triacylglycerols, nonesterified fatty acids, and waist circumference were significantly different between genotypes for 2 SNPs (rs266729 in ADIPOQ and rs10920533 in ADIPOR1). Minor allele homozygotes for both of these SNPs were identified as having degrees of insulin resistance, as measured by the homeostasis model assessment of insulin resistance, that were highly responsive to differences in plasma saturated fatty acids (SFAs). The SFA-dependent association between ADIPOR1 rs10920533 and insulin resistance was replicated in cases with MetS from a separate independent study, which was an association not present in controls. CONCLUSIONS: A reduction in plasma SFAs could be expected to lower insulin resistance in MetS subjects who are minor allele carriers of rs266729 in ADIPOQ and rs10920533 in ADIPOR1. Personalized dietary advice to decrease SFA consumption in these individuals may be recommended as a possible therapeutic measure to improve insulin sensitivity. This trial was registered at clinicaltrials.gov as NCT00429195.
  • Ferguson, Jane F., et al. (författare)
  • NOS3 gene polymorphisms are associated with risk markers of cardiovascular disease, and interact with omega-3 polyunsaturated fatty acids
  • 2010
  • Ingår i: Atherosclerosis. - 0021-9150 .- 1879-1484. ; 211:2, s. 539-544
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Omega-3 polyunsaturated fatty acids (n-3 PUFA) may protect against the development of cardiovascular disease (CVD). Genotype at key genes such as nitric oxide synthase (NOS3) may determine responsiveness to fatty acids. Gene-nutrient interactions may be important in modulating the development of CVD, particularly in high-risk individuals with the metabolic syndrome (MetS). Methods: Biomarkers of CVD risk, plasma fatty acid composition, and NOS3 single nucleotide polymorphism (SNP) genotype (rs11771443, rs1800783, rs1800779, rs1799983, rs3918227, and rs743507) were determined in 450 individuals with the MetS from the LIPGENE dietary intervention cohort. The effect of dietary fat modification for 12 weeks on metabolic indices of the MetS was determined to understand potential NOS3 gene-nutrient interactions. Results: Several markers of inflammation and dyslipidaemia were significantly different between the genotype groups. A significant gene-nutrient interaction was observed between the NOS3 rs1799983 SNP and plasma n-3 PUFA status on plasma triacylglycerol (TAG) concentrations. Minor allele carriers (AC + AA) showed an inverse association with significantly higher plasma TAG concentrations in those with low plasma n-3 PUFA status and vice versa but the major allele homozygotes (CC) did not. Following n-3 PUFA supplementation, plasma TAG concentrations of minor allele carriers of rs1799983 were considerably more responsive to changes in plasma n-3 PUFA, than major allele homozygotes. Conclusions: Carriers of the minor allele at rs1799983 in NOS3 have plasma TAG concentrations which are more responsive to n-3 PUFA. This suggests that these individuals might show greater beneficial effects of n-3 PUFA consumption to reduce plasma TAG concentrations.
  • Fjell, Anders M., et al. (författare)
  • Poor Self-Reported Sleep is Related to Regional Cortical Thinning in Aging but not Memory Decline-Results From the Lifebrain Consortium
  • 2021
  • Ingår i: Cerebral Cortex. - : Oxford University Press. - 1047-3211 .- 1460-2199. ; 31:4, s. 1953-1969
  • Tidskriftsartikel (refereegranskat)abstract
    • We examined whether sleep quality and quantity are associated with cortical and memory changes in cognitively healthy participants across the adult lifespan. Associations between self-reported sleep parameters (Pittsburgh Sleep Quality Index, PSQI) and longitudinal cortical change were tested using five samples from the Lifebrain consortium (n = 2205, 4363 MRIs, 18-92 years). In additional analyses, we tested coherence with cell-specific gene expression maps from the Allen Human Brain Atlas, and relations to changes in memory performance. "PSQI # 1 Subjective sleep quality" and "PSQI #5 Sleep disturbances" were related to thinning of the right lateral temporal cortex, with lower quality and more disturbances being associated with faster thinning. The association with "PSQI #5 Sleep disturbances" emerged after 60 years, especially in regions with high expression of genes related to oligodendrocytes and S1 pyramidal neurons. None of the sleep scales were related to a longitudinal change in episodic memory function, suggesting that sleep-related cortical changes were independent of cognitive decline. The relationship to cortical brain change suggests that self-reported sleep parameters are relevant in lifespan studies, but small effect sizes indicate that self-reported sleep is not a good biomarker of general cortical degeneration in healthy older adults.
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