This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Individuals with Familial Hypertriglyceridemia (FHTG) have elevated levels of triglycerides and normal total cholesterol. FHTG affects about 1% of the US population and is one of the most common genetic lipid disorders in patients with coronary artery disease. FHTG is thought to segregate as an autosomal dominant disorder but the single segregation analysis has not been conclusively replicated. The long-term objective of this proposal is to identify gene(s) that predispose individuals to FHTG using familial-based linkage analysis and determine how elevated levels of serum triglycerides and lipids predispose these individuals to atherosclerosis. We plan to accomplish the objective by pursuing the following two specific aims. 1. Identify Families with FHTG. We will identify probands through the statewide CARDIAC program and through a network of health clinics. 2. Identify FHTG susceptibility loci by linkage analysis on a genome-wide set of markers and on a small set of markers previously identified FHTG candidate loci. We will use linkage analysis methods to determine which loci contribute to FHTG in patients from the WV population and test for linkage and association with single nucleotide polymorphisms (SNPs) that are known to map to the regions of interest.The proposed work is innovative because we have access to patients in West Virginia who have not been studied. Our findings will be significant because they will further our undrstanding of the pathogenesis of vascular disease and because these susceptibility genes represent new targets for preventative and therapeutic interventions.
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