Project description:<p>The SEA study is a genome-wide association study to identify genetic variants associated with premature atherosclerosis in subjects included in the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) repository - a unique NHLBI resource including data, DNA and arterial specimens from over 3000 multi-ethnic subjects 15-34 years of age who died of non-atherosclerotic causes (mostly trauma). All PDAY subjects had post-mortem quantitative assessment of raised atherosclerotic lesions in their aorta and coronary arteries - making this the largest and most carefully phenotyped cohort for premature atherosclerosis in the world. The goal of the current project was to use the quantitative measure of raised atherosclerotic lesions in the PDAY cohort as the target phenotype for a genome-wide association study and to use quantitative measures of subclinical atherosclerosis (coronary calcium and carotid IMT) in the Multi-Ethnic Study of Atherosclerosis (MESA) to confirm or refute candidate loci identified from the PDAY analysis. Identifying genetic factors that predispose individuals to premature atherosclerosis could lead to more effective screening and early treatment of high risk individuals and suggest novel molecular targets for treatment and prevention interventions.</p>
Project description:<p>The SEA study is a genome-wide association study to identify genetic variants associated with premature atherosclerosis in subjects included in the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) repository - a unique NHLBI resource including data, DNA and arterial specimens from over 3000 multi-ethnic subjects 15-34 years of age who died of non-atherosclerotic causes (mostly trauma). All PDAY subjects had post-mortem quantitative assessment of raised atherosclerotic lesions in their aorta and coronary arteries - making this the largest and most carefully phenotyped cohort for premature atherosclerosis in the world. The goal of the current project was to use the quantitative measure of raised atherosclerotic lesions in the PDAY cohort as the target phenotype for a genome-wide association study and to use quantitative measures of subclinical atherosclerosis (coronary calcium and carotid IMT) in the Multi-Ethnic Study of Atherosclerosis (MESA) to confirm or refute candidate loci identified from the PDAY analysis. Identifying genetic factors that predispose individuals to premature atherosclerosis could lead to more effective screening and early treatment of high risk individuals and suggest novel molecular targets for treatment and prevention interventions.</p>
Project description:ApoC-III is a proatherogenic protein associated with elevated triglycerides; its deficiency is associated with reduced atherosclerosis. Mixed dyslipidemia, characterized by elevated triglyceride and apoC-III levels and low HDL cholesterol level, with or without elevated LDL cholesterol, increases cardiovascular disease risk and is commonly treated with combined statin and fibrate therapy. We sought to identify single nucleotide polymorphisms (SNPs) associated with apoC-III level response to combination therapy with statins and fenofibric acid (FA) in individuals with mixed dyslipidemia. Participants in a multicenter, randomized, double-blind, active-controlled study examining response to FA alone and in combination with statin were genotyped for candidate SNPs. Association between genotyed SNPs and APOC3 response to therapy was conducted
Project description:ApoC-III is a proatherogenic protein associated with elevated triglycerides; its deficiency is associated with reduced atherosclerosis. Mixed dyslipidemia, characterized by elevated triglyceride and apoC-III levels and low HDL cholesterol level, with or without elevated LDL cholesterol, increases cardiovascular disease risk and is commonly treated with combined statin and fibrate therapy. We sought to identify single nucleotide polymorphisms (SNPs) associated with apoC-III level response to combination therapy with statins and fenofibric acid (FA) in individuals with mixed dyslipidemia. Participants in a multicenter, randomized, double-blind, active-controlled study examining response to FA alone and in combination with statin were genotyped for candidate SNPs. Association between genotyed SNPs and APOC3 response to therapy was conducted We sought to identify single nucleotide polymorphisms (SNPs) associated with apoC-III level response to combination therapy with statins and fenofibric acid (FA) in individuals with mixed dyslipidemia. Participants in a multicenter, randomized, double-blind, active-controlled study examining response to FA alone and in combination with statin were genotyped for candidate SNPs. Genomic DNA extracted from peripheral blood was genotyped using a custom GoldenGate bead array encompassing 384 SNPs (Illumina). Multivariate linear regression and 2-way ANOVA for percent change in apoC-III level were performed between the groups receiving FA alone compared with FA+statin compared with statin alone.
Project description:This study is to compare the mRNA expression differences between atherosclerosis and non-atherosclerosis samples from female peripheral blood. The possible effects of races are also considered.