Metabolism and Genetics of Hypobetalipoproteinemia
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ABSTRACT: Hypobetalipoproteinemia is characterized by extremely low levels of low-density lipoprotein cholesterol. Familial hypobetalipoproteinemia (FHBL) is a monogenic form of hypobetalipoproteinemia caused by mutations in the APOB gene. There are cases of hypobetalipoproteinemia not caused by mutations in APOB, however. The purpose of this study is to identify novel genetic causes of hypobetalipoproteinemia.
SECONDARY ACCESSION(S): PRJNA178383PRJNA178384
REPOSITORIES: dbGaP
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Project description:<p>Hypobetalipoproteinemia is characterized by extremely low levels of low-density lipoprotein cholesterol. Familial hypobetalipoproteinemia (FHBL) is a monogenic form of hypobetalipoproteinemia caused by mutations in the APOB gene. There are cases of hypobetalipoproteinemia not caused by mutations in APOB, however. The purpose of this study is to identify novel genetic causes of hypobetalipoproteinemia.</p>
| phs000561.v1.p1 | EGA
Project description:Atherosclerosis is characterized by thickening of the arterial wall and is the primary cause of the coronary artery disease and cerebrovascular disease, two of the most common causes of illness and death worldwide. One of the leading risk factors for development of atherosclerosis is familial hypercholesterolemia. Familial hypercholesterolemia is an autosomal dominant disorder, which is caused by mutations mainly located in the low-density lipoprotein receptor (LDLR) gene. It is characterized by elevated levels of low-density lipoprotein cholesterol, the presence of tendon xanthomas, and premature cardiovascular disease. Aim of this study was to find atherosclerotic markers in white blood cells of patients compared to healthy controls. None of these patients exhibited symptoms of atherosclerosis by standard diagnostic methods; however, transcriptome analysis of blood RNA indicated changes in ubiquitin proteolysis and cell adhesion system as expected in initiation steps of atherosclerosis.
2008-12-18 | GSE13985 | GEO
Project description:Atherosclerosis is characterized by thickening of the arterial wall and is the primary cause of the coronary artery disease and cerebrovascular disease, two of the most common causes of illness and death worldwide. One of the leading risk factors for development of atherosclerosis is familial hypercholesterolemia. Familial hypercholesterolemia is an autosomal dominant disorder, which is caused by mutations mainly located in the low-density lipoprotein receptor (LDLR) gene. It is characterized by elevated levels of low-density lipoprotein cholesterol, the presence of tendon xanthomas, and premature cardiovascular disease. Aim of this study was to find atherosclerotic markers in white blood cells of patients compared to healthy controls. None of these patients exhibited symptoms of atherosclerosis by standard diagnostic methods; however, transcriptome analysis of blood RNA indicated changes in ubiquitin proteolysis and cell adhesion system as expected in initiation steps of atherosclerosis. Experiment Overall Design: Five patients diagnosed with Familial hypercholesterolemia and five age, sex, BMI and smoking status matched controls contributed blood from which total RNA from white blood cells was isolated. RNA samples were analyzed using Affymetrix microarrays and two groups were compared for differentially expressed genes.
2009-01-13 | E-GEOD-13985 | biostudies-arrayexpress
Project description:<p>The NHLBI "Grand Opportunity" Exome Sequencing Project (GO-ESP), a signature project of the NHLBI Recovery Act investment, was designed to identify genetic variants in coding regions (exons) of the human genome (the "exome") that are associated with heart, lung and blood diseases. These and related diseases that are of high impact to public health and individuals from diverse racial and ethnic groups will be studied. These data may help researchers understand the causes of disease, contributing to better ways to prevent, diagnose, and treat diseases, as well as determine whether to tailor prevention and treatments to specific populations. This could lead to more effective treatments and reduce the likelihood of side effects. GO-ESP is comprised of five collaborative components: 3 cohort consortia - HeartGO, LungGO, and WHISP - and 2 sequencing centers - BroadGO and SeattleGO.</p> <p>In this study, we seek to identify the genetic cause of two monogenic lipid disorders-severe hypercholesterolemia and familial hypoalphalipoproteinemia. Monogenic severe hypercholesterolemia is clinically characterized by elevated total and low-density lipoprotein (LDL) cholesterol levels in plasma. Elevated LDL-cholesterol levels lead to excessive deposition of cholesterol in arterial walls, which eventually results in accelerated atherosclerosis and premature cardiovascular disease (CVD). Monogenic hypercholesterolemia has a prevalence of approximately one in 500 individuals, making it one of the most common inherited disorders. To date, mutations in the LDL receptor (LDLR) ligand-binding domains of APOB and PCSK9 have been shown to cause hypercholesterolemia. While mutations in these genes can explain a large percentage of clinically diagnosed patients, the underlying molecular determinant in a substantial fraction of patients remains unknown.</p> <p>Familial hypoalphalipoproteinemia (low HDL-C) is defined by an HDL-C below the age- and sex- specific 10th percentile. ABCA1, LCAT, and APOA1 are known to cause familial hypoalphalipoproteinemia. We hypothesize that: (1) additional novel genes responsible for Mendelian forms of low HDL-C exist; and (2) the causal gene and mutation(s) in each family may be discovered with exome analysis of just a few affected individuals in each pedigree.</p>
| phs000587 | dbGaP
Project description:The hypocholesterolemic effect of probiotics has been observed, but the molecular mechanism of probiotic-host interaction is still obscure. In this study, DNA microarray technology was used to explore the gene expression profile of liver of hypercholesterolemic rats caused by administration of probiotic Lactobacillus casei Zhang, which can decrease the serum triglyceride, low-density lipoprotein cholesterol, hepatic cholesterol and triglyceride of hypercholesterolemic rats.
2011-12-31 | GSE23740 | GEO
Project description:Treatment with statins lowers low-density lipoprotein cholesterol for prevention of cardiovascular disease. We hypothesized major cardiac effects of statins.
2018-10-03 | GSE102666 | GEO
Project description:The hypocholesterolemic effect of probiotics has been observed, but the molecular mechanism of probiotic-host interaction is still obscure. In this study, DNA microarray technology was used to explore the gene expression profile of liver of hypercholesterolemic rats caused by administration of probiotic Lactobacillus casei Zhang, which can decrease the serum triglyceride, low-density lipoprotein cholesterol, hepatic cholesterol and triglyceride of hypercholesterolemic rats. Six liver samples in high fat and probiotic treated group (3 samples in each group) were randomly selected for RNA isolation and microarray hybridization, the 3 samples in high fat group were used as control.
2011-12-31 | E-GEOD-23740 | biostudies-arrayexpress
Project description:Morgan2016 - Dynamics of cholesterol
metabolism and ageing
This model is described in the article:
Mathematically modelling the
dynamics of cholesterol metabolism and ageing.
Morgan AE, Mooney KM, Wilkinson SJ,
Pickles NA, Mc Auley MT.
BioSystems 2016 Jul; 145: 19-32
Abstract:
Cardiovascular disease (CVD) is the leading cause of
morbidity and mortality in the UK. This condition becomes
increasingly prevalent during ageing; 34.1% and 29.8% of males
and females respectively, over 75 years of age have an
underlying cardiovascular problem. The dysregulation of
cholesterol metabolism is inextricably correlated with
cardiovascular health and for this reason low density
lipoprotein cholesterol (LDL-C) and high density lipoprotein
cholesterol (HDL-C) are routinely used as biomarkers of CVD
risk. The aim of this work was to use mathematical modelling to
explore how cholesterol metabolism is affected by the ageing
process. To do this we updated a previously published
whole-body mathematical model of cholesterol metabolism to
include an additional 96 mechanisms that are fundamental to
this biological system. Additional mechanisms were added to
cholesterol absorption, cholesterol synthesis, reverse
cholesterol transport (RCT), bile acid synthesis, and their
enterohepatic circulation. The sensitivity of the model was
explored by the use of both local and global parameter scans.
In addition, acute cholesterol feeding was used to explore the
effectiveness of the regulatory mechanisms which are
responsible for maintaining whole-body cholesterol balance. It
was found that our model behaves as a hypo-responder to
cholesterol feeding, while both the hepatic and intestinal
pools of cholesterol increased significantly. The model was
also used to explore the effects of ageing in tandem with three
different cholesterol ester transfer protein (CETP) genotypes.
Ageing in the presence of an atheroprotective CETP genotype,
conferring low CETP activity, resulted in a 0.6% increase in
LDL-C. In comparison, ageing with a genotype reflective of high
CETP activity, resulted in a 1.6% increase in LDL-C. Thus, the
model has illustrated the importance of CETP genotypes such as
I405V, and their potential role in healthy ageing.
This model is hosted on
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and identified by:
MODEL1508170000.
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To the extent possible under law, all copyright and related or
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2017-06-01 | MODEL1508170000 | BioModels
Project description:In this study, the contribution of cholesterol uptake by the low-density-lipoprotein receptor (LDLR) in the metabolic reprogramming of activated T cells was investigated at proteome level by mass-spectrometry-assisted shotgun proteomics.
2022-09-20 | PXD030365 | Pride
Project description:The high-fat diet (HFD)-feeding significantly stimulated hypercholesterolemia in male SD rats. Simultaneous feeding of hawk tea extracts (HTE) reversed the hypercholesterolemia in rats by lowering the serum total cholesterol and low-density lipoprotein cholesterol levels. To understand the molecular mechanism underlying the cholesterol-lowering effects of HTE, we performed the RNA-seq analysis. Consequently, the change in mRNA levels of genes invovled in metabolism of lipid and lipoprotein, primary bile acid synthesis, and ABC transporters itriggered by HFD-feeding were reversed by the co-administration of HTE (200 mg/kg/day for 11 weeks).
2019-05-21 | GSE125084 | GEO