Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Evidence of mechanism how rs7575840 influences apolipoprotein B containing lipid particles

ABSTRACT: Objective: Recent genome-wide association studies (GWAS) identified a variant rs7575840 in the apolipoprotein B (APOB) gene region to be associated with LDL-C. However, the underlying functional mechanism of this variant that resides 6.5 kb upstream of APOB has remained unknown. Our objective was to investigate rs7575840 for association with refined apoB containing lipid particles; for replication in a non-Caucasian Mexican population; and for underlying functional mechanism. Methods and Results Our data show that rs7575840 is associated with serum apoB levels (P=4.85x10-10) and apoB containing lipid particles, very small VLDL, IDL and LDL particles (P=2x10-5 - 9x10-7) in the Finnish METSIM study sample (n=7,710). Fine mapping of the APOB region using 43 SNPs replicated the association of rs7575840 with apoB in a Mexican study sample (n=2,666, P=3.33x10-05). Furthermore, our transcript analyses of adipose RNA samples from 175 Finnish METSIM subjects indicate that rs7575840 alters expression of APOB (P=1.13x10-10) and a regional non-coding RNA (BU630349) (P=7.86x10-6) in adipose tissue. Conclusions It has been difficult to convert GWAS associations into mechanistic insights. Our data show that rs7575840 is associated with serum apoB levels and apoB containing lipid particles as well as influences expression of APOB and a regional transcript BU630349 in adipose tissue. We thus provide evidence how a common genome-wide significant SNP rs7575840 may affect serum apoB, LDL-C, and TC levels.

ORGANISM(S): Homo sapiens

PROVIDER: GSE27666 | GEO | 2011/09/01

SECONDARY ACCESSION(S): PRJNA138477

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Evidence of mechanism how rs7575840 influences apolipoprotein B containing lipid particles

Project description:Objective: Recent genome-wide association studies (GWAS) identified a variant rs7575840 in the apolipoprotein B (APOB) gene region to be associated with LDL-C. However, the underlying functional mechanism of this variant that resides 6.5 kb upstream of APOB has remained unknown. Our objective was to investigate rs7575840 for association with refined apoB containing lipid particles; for replication in a non-Caucasian Mexican population; and for underlying functional mechanism. Methods and Results Our data show that rs7575840 is associated with serum apoB levels (P=4.85x10-10) and apoB containing lipid particles, very small VLDL, IDL and LDL particles (P=2x10-5 - 9x10-7) in the Finnish METSIM study sample (n=7,710). Fine mapping of the APOB region using 43 SNPs replicated the association of rs7575840 with apoB in a Mexican study sample (n=2,666, P=3.33x10-05). Furthermore, our transcript analyses of adipose RNA samples from 175 Finnish METSIM subjects indicate that rs7575840 alters expression of APOB (P=1.13x10-10) and a regional non-coding RNA (BU630349) (P=7.86x10-6) in adipose tissue. Conclusions It has been difficult to convert GWAS associations into mechanistic insights. Our data show that rs7575840 is associated with serum apoB levels and apoB containing lipid particles as well as influences expression of APOB and a regional transcript BU630349 in adipose tissue. We thus provide evidence how a common genome-wide significant SNP rs7575840 may affect serum apoB, LDL-C, and TC levels. 175 samples, no replicates

2011-08-31 | E-GEOD-27666 | biostudies-arrayexpress

siRNAs induced long-term liver ApoB mRNA knockdown significantly lowers serum cholesterol in a mouse model with human-like serum lipids

Project description:Increased serum apoB and associated low density lipoprotein cholesterol (LDL) levels are well correlated with an increased risk of coronary disease. Apo E-/- and LDLr -/- mice have been extensively used for studies of coronary atherosclerosis. These animals show atherosclerotic lesions similar to those in humans, but their serum lipids are low in apoB containing LDL particles. We describe the development of a new mouse model with a human-like lipid profile. Ldlr+/- CETP+/- hemizygous mice carry a single copy of the human CETP transgene and a single copy of a LDL receptor mutation. To evaluate the apoB pathways in this mouse model, we used novel siRNAs formulated in lipid nanoparticles (LNPs). ApoB siRNAs induced up to 95% reduction of liver ApoB mRNA and serum apoB protein, and a significant lowering of serum LDL in Ldlr+/- CETP+/- mice. ApoB targeting is specific, dose dependent and shows lipid lowering effects for over three weeks. Although specific TGs were affected by ApoB KD, and the total plasma lipid levels were decreased by 70%, the overall lipid distribution did not change. Results presented here demonstrate a new mouse model for investigating additional targets within the ApoB pathways using the siRNA modality.

2010-11-22 | GSE23088 | GEO

siRNAs induced long-term liver ApoB mRNA knockdown significantly lowers serum cholesterol in a mouse model with human-like serum lipids

2010-11-22 | E-GEOD-23088 | biostudies-arrayexpress

Epigenome-wide association in the METSIM cohort identifies 22 novel loci for diabetes and metabolic syndrome traits

Project description:In this study, we examined the association of DNA methylation with metabolic traits in humans using adipose tissue samples from the Metabolic Syndrome in Men (METSIM) cohort. The METSIM cohort has been thoroughly characterized for longitudinal clinical data of metabolic traits including a 3-point oral glucose tolerance test, cardiovascular disorders, diabetes complications, drug and diet questionnaire, as well as high density genotyping, and genome-wide expression in adipose. We performed epigenome-wide association studies on clinical traits using reduced representation bisulfite sequencing data and identified 61 signifiant associations for metabolic syndrome traits, corresponding to 25 unique loci. These associations include previously known genes, FASN, RXRA, MSH2, and MSH6, as well as 22 loci harboring 18 new candidate genes for diabetes and obesity in humans.

2017-01-01 | GSE87893 | GEO

Gene expression analysis of subcutaneous and omental adipose tissue from obese, insulin-resistant women

Project description:The association between central obesity and insulin resistance reflects the properties of visceral adipose tissue. Our aim was to gain further insight into this association by analysing the lipid composition of subcutaneous and omental adipose tissue in obese women with and without insulin resistance. Subcutaneous and omental adipose tissue and serum were obtained from 29 obese nondiabetic women, 13 of whom were hyperinsulinemic. Histology, and lipid and gene profiling were performed. In omental adipose tissue of obese, insulin-resistant women, adipocyte hypertrophy and macrophage infiltration were accompanied by an increase in GM3 ganglioside and its synthesis enzyme ST3GAL5; in addition, phosphatidylethanolamine (PE) lipids were increased and their degradation enzyme, PEMT, decreased. ST3GAL5 was expressed predominantly in adipose stromovascular cells and PEMT in adipocytes. Insulin resistance was also associated with an increase in PE lipids in serum.

2015-12-07 | GSE73108 | GEO

Gene expression analysis of subcutaneous and omental adipose tissue from obese, insulin-resistant women

2015-12-07 | E-GEOD-73108 | biostudies-arrayexpress

Hyperglycemia and a Common Variant of GCKR Are Associated with the Levels of Eight Amino Acids in 9,371 Finnish Men

Project description:Objective: Insulin regulates amino acid metabolism. We investigated whether glycemia and 43 genetic risk variants for hyperglycemia/type 2 diabetes affect amino acid levels in a large population-based cohort. Subjects and Methods: A total of 9,371 non-diabetic or newly-diagnosed type 2 diabetic Finnish men from the population-based METSIM Study were studied. Proton NMR spectroscopy was used to measure plasma levels of 8 amino acids. Genotyping of 42 SNPs and mRNA microarray analysis from 200 subcutaneous adipose tissue samples were performed. Results: Increasing fasting and/or 2-hour plasma glucose levels were associated with increasing levels of alanine, valine, leucine, isoleucine, phenylalanine and tyrosine, and decreasing levels of histidine and glutamine. We also found significant correlations between insulin sensitivity (Matsuda ISI) and expression of genes regulating amino acid metabolism. Only one SNP (rs780094 in GCKR) of the 42 risk SNPs for type 2 diabetes or hyperglycemia was significantly associated with the levels of alanine, isoleucine, and glutamine. Conclusions : We observed that the levels of branched-chain, aromatic amino acids and alanine increased and the levels of glutamine and histidine decreased with increasing glycemia. These associations seemed to be mediated by insulin resistance, at least in part. GCKR rs780094 was significantly associated with several amino acids. Total RNA was obtained from subcutaneous fat biopsies from 200 people participating in the METSIM study (4 samples were replicated for a total of 204 arrays).

2012-04-01 | E-GEOD-32512 | biostudies-arrayexpress

RNA-sequencing of ApoB-reactive CD4+ T cells in mice

Project description:We report the transcriptome of atherosclerosis-specific murine CD4+ T cells in atherosclerosis that recognize a peptide from ApoB-100, the core protein of low-density lipoprotein (LDL). Our data reveal a unique transcriptome of ApoB-specific T cells that is similar to T-regulatory T cells and changes during disease progression in a pathogenic T-helper type -1 and -17 like transcriptome.

2020-05-21 | GSE149067 | GEO

Single-nucleus RNA sequencing of human subcutaneous adipose tissue biopsies from 16 Finnish participants.

Project description:Single-nucleus RNA-seq was performed to characterize the transcriptomes of cell types in human subcutaneous adipose tissue. Biopsies from 16 Finnish participants from the Finnish Twin Study and CRYO study were included.

2023-07-22 | GSE236708 | GEO

Apolipoprotein F in hyperlipidemia

Project description:Apolipoprotein F (ApoF) modulates lipoprotein metabolism by selectively inhibiting cholesteryl ester transfer protein (CETP) activity on LDL. This ApoF activity requires that it is bound to LDL. How hyperlipidemia alters total plasma ApoF and its binding to LDL are poorly understood. In this study, total ApoF and LDL-bound ApoF were quantified by ELISA. Plasma ApoF is increased 34% in hypercholesterolemic plasma. In hypertriglyceridemic plasma, ApoF was statistically unchanged. However, in donors with combined hypercholesterolemia and hypertriglyceridemia, the elevated triglyceride ameliorated the rise in ApoF caused by hypercholesterolemia alone. Compared to normolipidemic LDL, hypercholesterolemic LDL contained ~2-fold more ApoF per LDL particle, whereas ApoF bound to LDL in hypertriglyceridemia plasma was < 20% of control. To understand the basis for altered association of ApoF with hyperlipidemic LDL, the physiochemical properties of LDL were modified in vitro by CETP ± LCAT activities. The time-dependent change in LDL lipid composition, proteome, core and surface lipid packing, LDL surface charge, and LDL size caused by these factors were compared with the ApoF binding capacity of these LDL. Only LDL particle size correlated with ApoF binding capacity. This positive association between LDL size and ApoF content was confirmed in hyperlipidemic plasmas. Similarly, when in vitro-produced, enlarged LDL with elevated ApoF binding capacity were incubated with LPL to reduce their size, ApoF binding was reduced by 90%. Thus, plasma ApoF levels and the activation status of this ApoF are differentially altered by hypercholesterolemia and hypertriglyceridemia. LDL size is a key determinate of ApoF binding and activation.

2022-02-11 | PXD029713 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data