Track topics on Twitter Track topics that are important to you
To investigate the role in coronary heart disease (CHD) of intragenic variation in a network of six genes affecting lipoprotein transport and metabolism.
In recent years, a number of candidate genetic variants (e.g., single nucleotide polymorphisms, SNPs) have been reported to be associated with coronary heart disease (CHD). However, these association studies have suffered from variability and failures of replication. This may result in part from selection of marker SNPs in linkage disequilibrium (LD) with true disease-related SNPs or with other effect-modulating genetic variants. Other issues include the play of chance in samples of limited size, population stratification artifacts, and small effect size for single SNPs. A recent discovery is that the genome is organized into largely invariant DNA fragments at the population level characterized by infrequent recombination events interspersed with "hotspots" of recombination and designated "haplotype blocks". These haplotype blocks can be determined by creating a dense map of SNPs across the gene of interest and analyzing population level LD. A few SNPs then can be chosen that designate ("tag") each haplotype block and used to comprehensively assess disease associations across the entire gene. Applying this approach to multiple genes in pathways critical to vascular health and assessing combinations of genes is likely to increase the power to discover genetic associations with CHD risk.
The study will establish high density SNP maps across exons, splice regions, and 5' and 3' regulatory regions of 6 genes that play key roles in lipoprotein transport and metabolism (ABCA1, CETP, LCAT, HL, LPL, SRB1); introns will be examined for 2 of the genes (CETP, LPL). By analyzing combinations of haplotype-tagging (ht) SNPs, "genetic burden" can be scored and correlated with CHD risk at 4 levels: 1) biomarker (lipid/lipoprotein levels), 2) anatomic (angiographic) CHD, 3) clinical outcome (death/MI), and 4) (exploratory) response to lipid-lowering. Testing will be performed in 3 large, distinct, but complementary Utah populations at primary or secondary risk of premature CHD. Testing will occur in 2 stages to establish reproducibility: an initial screening phase followed by a confirmation phase (for genetic markers and combinations showing promise) in a larger, independent sample. The study will employ novel methods that combine high-throughput SNP discovery and genotyping capability with genetic epidemiological methods to identify the haplotype blocks within and surrounding the genes of interest, identify htSNPs, and assess disease associations with individual and combinations of htSNPs ("genetic burden"). To this, the study brings large, well characterized databases, assembled and followed for up to 9 years, which will be further expanded under the current project.
National Heart, Lung, and Blood Institute (NHLBI)
Published on BioPortfolio: 2014-08-27T03:54:05-0400
To determine the factors associated with progression of sub-clinical atherosclerosis and to evaluate the associations between the progression of sub-clinical atherosclerosis and the develo...
Atherosclerosis vaccine, V6, has been through two small-scale Phase II open label clinical trials. It has shown significant improvement in lipid profile in patients with overweight or obes...
To evaluate common genetic variations, that in combination with exposure to tobacco smoke, may modify the risk of atherosclerosis.
To measure by gas-liquid chromatography the relative concentrations of all saturated and unsaturated fatty acids found in the cholesterol ester and phospholipid fractions of plasma from 4,...
The purpose of this study is to determine the effects of estrogen replacement therapy (ERT) on the progression of early atherosclerosis in healthy postmenopausal women without preexisting ...
Leukocytosis, particularly monocytosis, has been shown to promote atherosclerosis in both diabetic and non-diabetic mouse models. We previously showed that hyperglycemia independently promotes monocyt...
In a previous work, a female-specific atherosclerosis risk locus on chromosome (Chr) 3 was identified in an intercross of atherosclerosis-resistant FVB and atherosclerosis-susceptible C57BL/6 (B6) mic...
Hepatocyte growth factor (HGF) has previously been associated with risk of stroke, coronary heart disease, and atherosclerosis. We hypothesized that higher circulating HGF is associated with greater p...
Vascular biglycan contributes to atherosclerosis development and increased biglycan expression correlates with increased atherosclerosis. However, mice deficient in biglycan have either no reduction i...
Lack of perfusion in the EXTREMITIES resulting from atherosclerosis. It is characterized by INTERMITTENT CLAUDICATION, and an ANKLE BRACHIAL INDEX of 0.9 or less.
Complete blockage of blood flow through one of the CORONARY ARTERIES, usually from CORONARY ATHEROSCLEROSIS.
A drug that has been given by mouth in the treatment of atherosclerosis and other vascular disorders, hyperlipidemias, and thrombo-embolic disorders. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1408)
A measurement of the thickness of the carotid artery walls. It is measured by B-mode ULTRASONOGRAPHY and is used as a surrogate marker for ATHEROSCLEROSIS.
Abnormal balloon- or sac-like dilatation in the wall of CORONARY VESSELS. Most coronary aneurysms are due to CORONARY ATHEROSCLEROSIS, and the rest are due to inflammatory diseases, such as KAWASAKI DISEASE.
Clinical Approvals Clinical Trials Drug Approvals Drug Delivery Drug Discovery Generics Drugs Prescription Drugs In the fields of medicine, biotechnology and pharmacology, drug discovery is the process by which drugs are dis...
Bioinformatics is the application of computer software and hardware to the management of biological data to create useful information. Computers are used to gather, store, analyze and integrate biological and genetic information which can then be applied...