Project Number: 1950-51520-010-02
Project Type: Specific Cooperative Agreement

Start Date: Oct 01, 2006
End Date: Sep 30, 2011

Objective:
To identify genetic markers for assessment of cardiovascular health related to plasma lipoprotein levels, diabetes and obesity and evaluate, the effects of specific gene-gene interactions in common metabolic pathways. To investigate the interactions between genetics and nutrients in the development of cardiovascular disease (CVD), the major age-related disorder affecting life expectancy and quality of life in the United States (US). Emphasis is placed on elucidating mechanisms by which genetic variation interacts with dietary and behavioral factors to regulate the homeostasis of the cardiovascular system. To identify genes newly associated with cardiovascular health and overall longevity and determine their expression response to dietary intervention using animal models of aging.

Approach:
Because the response of the individual to nutrients contains a strong genetic component, our approach aims to uncover sets of genes involved in the dietary response and to describe specific gene-diet interactions. This will be tested using high throughput genotyping technics, both in ongoing studies of free-living populations and in the metabolic ward (intervention studies). Our primary focus is to describe gene-diet interactions affecting/influencing progression of the metabolic syndrome, in particular obesity, often a precursor to cardiovascular disease and diabetes. Cardiovascular candidate genes, both those previously described in the literature as well as those we identify through bioinformatics analysis, will be used to examine associations and interactions on various scales. These include genetic variations, disease-related phenotypes, and specific nutrients [fatty acids, cholesterol, plant sterols) and behavioral habits (alcohol consumption, smoking, physical (in)activity]. Rigorous statistical analysis will uncover the associations between phenotypes indicative of increased risk of metabolic syndrome and the genes responsible for such. Because cardiovascular disease and diabetes are traditionally considered diseases of the aged, we will also continue with our investigations to identify genes responsible for healthy aging. The principal approach taken for these studies involves gene expression microarray analysis of fruit fly D. melanogaster populations with a propensity for increased longevity. Candidate aging genes will then be studied in mammalian models as well in human populations.