Sök i SwePub databas

  Utökad sökning

Träfflista för sökning "L773:1942 325X OR L773:1942 3268 "

Sökning: L773:1942 325X OR L773:1942 3268

  • Resultat 1-10 av 61
  • [1]234567Nästa
Sortera/gruppera träfflistan
  • Pfeiffer, L., et al. (författare)
  • DNA methylation of lipid-related genes affects blood lipid levels
  • 2015
  • Ingår i: Circ Cardiovasc Genet. - 1942-3268 (Electronic) 1942-3268 (Linking) ; 8:2, s. 334-42
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Epigenetic mechanisms might be involved in the regulation of interindividual lipid level variability and thus may contribute to the cardiovascular risk profile. The aim of this study was to investigate the association between genome-wide DNA methylation and blood lipid levels high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, and total cholesterol. Observed DNA methylation changes were also further analyzed to examine their relationship with previous hospitalized myocardial infarction. METHODS AND RESULTS: Genome-wide DNA methylation patterns were determined in whole blood samples of 1776 subjects of the Cooperative Health Research in the Region of Augsburg F4 cohort using the Infinium HumanMethylation450 BeadChip (Illumina). Ten novel lipid-related CpG sites annotated to various genes including ABCG1, MIR33B/SREBF1, and TNIP1 were identified. CpG cg06500161, located in ABCG1, was associated in opposite directions with both high-density lipoprotein cholesterol (beta coefficient=-0.049; P=8.26E-17) and triglyceride levels (beta=0.070; P=1.21E-27). Eight associations were confirmed by replication in the Cooperative Health Research in the Region of Augsburg F3 study (n=499) and in the Invecchiare in Chianti, Aging in the Chianti Area study (n=472). Associations between triglyceride levels and SREBF1 and ABCG1 were also found in adipose tissue of the Multiple Tissue Human Expression Resource cohort (n=634). Expression analysis revealed an association between ABCG1 methylation and lipid levels that might be partly mediated by ABCG1 expression. DNA methylation of ABCG1 might also play a role in previous hospitalized myocardial infarction (odds ratio, 1.15; 95% confidence interval=1.06-1.25). CONCLUSIONS: Epigenetic modifications of the newly identified loci might regulate disturbed blood lipid levels and thus contribute to the development of complex lipid-related diseases.
  • Ali, Ashfaq, et al. (författare)
  • Do Genetic Factors Modify the Relationship Between Obesity and Hypertriglyceridemia? : Findings From the GLACIER and the MDC Studies
  • 2016
  • Ingår i: Circulation. - : American Heart Association. - 1942-325X .- 1942-3268. ; 9:2, s. 162-171
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Obesity is a major risk factor for dyslipidemia, but this relationship is highly variable. Recently published data from 2 Danish cohorts suggest that genetic factors may underlie some of this variability.Methods and Results We tested whether established triglyceride-associated loci modify the relationship of body mass index (BMI) and triglyceride concentrations in 2 Swedish cohorts (the Gene-Lifestyle Interactions and Complex Traits Involved in Elevated Disease Risk [GLACIER Study; N=4312] and the Malmo Diet and Cancer Study [N=5352]). The genetic loci were amalgamated into a weighted genetic risk score (WGRS(TG)) by summing the triglyceride-elevating alleles (weighted by their established marginal effects) for all loci. Both BMI and the WGRS(TG) were strongly associated with triglyceride concentrations in GLACIER, with each additional BMI unit (kg/m(2)) associated with 2.8% (P=8.4x10(-84)) higher triglyceride concentration and each additional WGRS(TG) unit with 2% (P=7.6x10(-48)) higher triglyceride concentration. Each unit of the WGRS(TG) was associated with 1.5% higher triglyceride concentrations in normal weight and 2.4% higher concentrations in overweight/obese participants (P-interaction=0.056). Meta-analyses of results from the Swedish cohorts yielded a statistically significant WGRS(TG)xBMI interaction effect (P-interaction=6.0x10(-4)), which was strengthened by including data from the Danish cohorts (P-interaction=6.5x10(-7)). In the meta-analysis of the Swedish cohorts, nominal evidence of a 3-way interaction (WGRS(TG)xBMIxsex) was observed (P-interaction=0.03), where the WGRS(TG)xBMI interaction was only statistically significant in females. Using protein-protein interaction network analyses, we identified molecular interactions and pathways elucidating the metabolic relationships between BMI and triglyceride-associated loci.Conclusions Our findings provide evidence that body fatness accentuates the effects of genetic susceptibility variants in hypertriglyceridemia, effects that are most evident in females.
  • Berg, Katarina, et al. (författare)
  • Elevated CD14++CD16- Monocytes Predict Cardiovascular Events.
  • 2012
  • Ingår i: Circulation: Cardiovascular Genetics. - : American Heart Association. - 1942-325X .- 1942-3268. ; 5:1, s. 122-131
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: -Although monocytes in peripheral blood are no longer considered to be a homogeneous population, associations between distinct monocyte subsets and cardiovascular disease have not been highlighted in large epidemiological studies. METHODS AND RESULTS: -The study included 700 randomly selected subjects from the cardiovascular arm of the Malmö Diet and Cancer study. Among these, 123 subjects suffered ischemic cardiovascular events during the follow-up until December 2008. Mononuclear leukocytes frozen at the baseline investigation in 1991-94 were thawed and analyzed with flow cytometry to enumerate monocyte subsets based on CD14 and CD16 expression. The percentage and number of classical CD14(++)CD16(-) monocytes were increased in the cardiovascular-event group compared to the event-free subjects (median 69% (inter-quartile range 62-76)% vs. 67 (59-72)%, p=0.017; 344 (251-419) cells/μL vs. 297 (212-384) cells/μL, p=0.003). The hazard ratio was 1.66 for suffering a cardiovascular event in the highest tertile of the number of CD14(++)CD16(-) monocytes compared to the lowest tertile even after adjustment for common risk factors (HR 1.66, 95%CI: 1.02-2.72). CD14(++)CD16(-) monocytes did not, however, associate with the extent of atherosclerosis at baseline. In contrast, the percentage of monocytes expressing CD16 was negatively associated to the extent of carotid atherosclerosis measured as intima-media thickness (IMT) at baseline. The chemokine receptors CCR2, CX3CR1 and CCR5 were not differentially expressed between cases and controls on any of the monocyte subsets, but CCR5 expression on CD14(+)CD16(++) monocytes was negatively associated to carotid IMT. CONCLUSIONS: -This study shows that classical CD14(++)CD16(-) monocytes can predict future cardiovascular risk independently of other risk factors in a randomly selected population.
  • Boardman-Pretty, Freya, et al. (författare)
  • Functional Analysis of a Carotid Intima-Media Thickness Locus Implicates BCAR1 and Suggests a Causal Variant.
  • 2015
  • Ingår i: Circulation: Cardiovascular Genetics. - : American Heart Association. - 1942-325X .- 1942-3268. ; 8:5, s. 696-706
  • Tidskriftsartikel (refereegranskat)abstract
    • -Carotid intima-media thickness (cIMT) is a marker of subclinical atherosclerosis that can predict cardiovascular disease (CVD) events over traditional risk factors. This study examined the BCAR1-CFDP1-TMEM170A locus on chromosome 16, associated with cIMT and coronary artery disease in the IMPROVE cohort, to identify the functional variant.
  • Chu, A. Y., et al. (författare)
  • Differential Genetic Effects on Statin-Induced Changes Across Low-Density Lipoprotein-Related Measures
  • 2015
  • Ingår i: Circulation: Cardiovascular Genetics. - 1942-325X .- 1942-3268. ; 8:5, s. 688-695
  • Tidskriftsartikel (refereegranskat)abstract
    • Background-Statin therapy influences not only low-density lipoprotein (LDL) cholesterol levels but also LDL-related biomarkers, including non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B, total number of LDL particles, and mean LDL particle size. Recent studies have identified many genetic loci influencing circulating lipid levels and statin-induced LDL cholesterol reduction. However, it is unknown how these genetic variants influence statin-induced changes in LDL subfractions and non-HDL-C. Methods and Results-One hundred sixty candidate single-nucleotide polymorphisms for effects on circulating lipid levels or statin-induced LDL-cholesterol lowering were tested for association with response of LDL subfractions and non-HDL-C to rosuvastatin or placebo for 1 year among 7046 participants from the Justification for Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial. Of the 51 single-nucleotide polymorphisms associated with statin response for ≥1 of the LDL subfractions or non-HDL-C, 20 single-nucleotide polymorphisms could be clustered according to effects predominantly on LDL particle size, predominantly on LDL particle number, and on apolipoprotein B but not on LDL cholesterol or non-HDL-C. Conclusions-These differential associations point to pathways of LDL response to statin therapy and possibly to mechanisms of statin-dependent cardiovascular disease risk reduction. © 2015 American Heart Association, Inc.
  • Ekblom, Kim, 1970-, et al. (författare)
  • Plasma Bilirubin and UGT1A1*28 Are Not Protective Factors Against First-Time Myocardial Infarction in a Prospective, Nested Case–Referent Setting
  • 2010
  • Ingår i: Circulation. - Philadelphia, PA : Lippincott Williams & Wilkins. - 1942-325X .- 1942-3268. ; :3, s. 340-347
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Bilirubin, an effective antioxidant, shows a large variation in levels between individuals and has been positively associated with reduced cardiovascular disease risk. A major reason for the variability is a common promoter polymorphism, UGT1A1*28, which reduces the transcription of the enzyme that conjugates bilirubin, UDP-glucuronosyltransferase 1A1. The aim of the study was to evaluate a possible protective effect of plasma bilirubin and the UGT1A1*28 polymorphism against myocardial infarction in a prospective case-referent setting.Methods and Results: 618 subjects with a first-ever myocardial infarction (median event age 60.5 years, median lag time 3.5 years) and 1184 matched referents were studied. Plasma bilirubin was lower in cases vs. referents. Despite a strong gene-dosage effect on bilirubin levels in both cases and referents, the UGT1A1*28 polymorphism did not influence the risk of myocardial infarction. Among multiple other variables, serum iron showed one of the strongest associations with bilirubin levels.Conclusion: We found no evidence for a protective effect of the UGT1A1*28 polymorphism against myocardial infarction and consequently neither for bilirubin. The lower bilirubin levels in cases might be caused by decreased production, increased degradation or increased elimination.
  • Folkersen, Lasse, et al. (författare)
  • Association of genetic risk variants with expression of proximal genes identifies novel susceptibility genes for cardiovascular disease
  • 2010
  • Ingår i: Circulation. - 1942-325X .- 1942-3268. ; 3:4, s. 365-373
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Population-based genome-wide association studies have identified several single nucleotide polymorphisms (SNPs) associated with cardiovascular disease or its risk factors. Genes in close proximity to these risk-SNPs are often thought to be pathogenetically important based on their location alone. However, the actual connections between SNPs and disease mechanisms remain largely unknown. METHODS AND RESULTS: To identify novel susceptibility genes, we investigated how 166 SNPs previously found to be associated with increased cardiovascular risk and/or predisposing metabolic traits relate to the expression of nearby genes. Gene expression in 577 samples of aorta, liver, mammary artery, and carotid atherosclerotic plaque was measured using expression arrays. For 47 SNPs, the expression levels of proximal genes (located within 200 kb) were affected (P<0.005). More than 20 of these genes had not previously been identified as candidate genes for cardiovascular or related metabolic traits. SNP-associated gene effects were tissue-specific and the tissue specificity was phenotype-dependent. CONCLUSIONS: This study demonstrates several instances of association between risk-SNPs and genes immediately adjacent to them. It also demonstrates instances in which the associated gene is not the immediately proximal and obvious candidate gene for disease. This shows the necessity of careful studies of genetic marker data as a first step toward application of genome-wide association studies findings in a clinical setting.
Skapa referenser, mejla, bekava och länka
  • Resultat 1-10 av 61
  • [1]234567Nästa
Typ av publikation
tidskriftsartikel (61)
Typ av innehåll
refereegranskat (58)
övrigt vetenskapligt (3)
Melander, Olle (10)
Humphries, SE (7)
Folkersen, L (6)
Eriksson, P (6)
Samani, Nilesh J. (6)
Kivimaki, M (5)
visa fler...
Salomaa, Veikko (5)
Hallmans, Göran (5)
Hamsten, A (5)
Kumari, M (5)
Sundquist, Kristina (5)
Zöller, Bengt (5)
Varga, Tibor V (5)
Nyberg, Fredrik, 196 ... (5)
Samani, NJ (5)
Sandling, Johanna K (5)
Erdmann, J. (4)
Franks, Paul W (4)
Smith, Gustav (4)
Psaty, Bruce M. (4)
Rotter, Jerome I. (4)
Deloukas, Panos (4)
Syvänen, Ann-Christi ... (4)
Franco-Cereceda, A (4)
Ridker, P. M. (4)
Chasman, D. I. (4)
Shah, S (4)
Li, Xinjun (4)
Syvanen, AC (4)
Groop, Leif (3)
Lind, Lars (3)
Ferrucci, Luigi (3)
Gudnason, Vilmundur (3)
Uitterlinden, Andre ... (3)
Van Duijn, Cornelia ... (3)
Deary, Ian J. (3)
Hedblad, Bo (3)
Gertow, K (3)
Melander, O. (3)
Deloukas, P (3)
Sundquist, Jan (3)
Ridker, Paul M. (3)
Chasman, Daniel I. (3)
Langenberg, Claudia (3)
Hamsten, Anders (3)
Ingelsson, E (3)
Folkersen, Lasse (3)
Poveda, Alaitz (3)
Sandling, JK (3)
Palmer, Colin N. A. (3)
visa färre...
Lunds universitet (24)
Karolinska Institutet (21)
Uppsala universitet (13)
Umeå universitet (8)
Göteborgs universitet (6)
Linköpings universitet (2)
visa fler...
Örebro universitet (1)
Malmö universitet (1)
visa färre...
Engelska (61)
Forskningsämne (UKÄ/SCB)
Medicin och hälsovetenskap (40)
Naturvetenskap (1)


pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy