Latisha Love-Gregory, Ph.D
Project Overview:
Chronically elevated non-fasting lipid levels after a high-fat meal are linked to the progression of atherosclerosis and are a clinically significant risk factor for cardiovascular disease and stroke. Current therapeutic guidelines focus on reducing blood triglyceride and low-density lipoprotein cholesterol (LDL-C) concentrations to reduce cardiovascular events. However, there is a need for the development of early risk assessment tools to identify individuals at high disease risk and to improve long-term health outcomes.
The purpose of this study is to determine the functional relevance of genetic variants in the CD36 gene (encodes a protein that facilitates tissue uptake of dietary fat). Common variants in the CD36 gene associate with variability in fasting lipid levels and with the risk of metabolic syndrome (MetS) and stroke. Studies in humans and in rodent models implicate CD36 in insulin resistance and proinflammatory processes linking the gene to atherosclerosis; however, information regarding the effect of genetic variants on expression of CD36 and how this influences the body’s ability to handle dietary fat are very few.
During the first year of funding, we determined that the common (allele frequencies >20%) CD36 SNPs (single nucleotide polymorphisms) associate with the risk of MetS also increase blood cholesterol and triglycerides in response to a high-fat meal. This would suggest that these SNPs might alter regulation of CD36 and influence the processing of ingested fat, which would promote abnormalities of blood lipids.
We now propose to: 1) determine the effects of the SNPs on CD36 levels and how they are regulated by dietary fat; and 2) determine how the SNPs identified in this study influence CD36 levels in adipose and muscle tissue, where most of the fat from the diet is processed.
The studies we proposed would provide functional evidence and strong rationales for the use of these common SNPs as genetic biomarkers to identify individuals with high susceptibility to lipid abnormalities and associated diseases. Genetic biomarkers such as the CD36 variants would be helpful for very early assessment of disease susceptibility, which allows optimization of preventive approaches that improve long-term health.
Final Report:
An individual’s risk of cardiovascular disease (CVD) and stroke reflects complex interactions between genetic, dietary and lifestyle influences. Chronically elevated cholesterol and triglyceride levels after a meal are risk factors for CVD and stroke. Current therapeutic guidelines focus on reducing blood triglyceride and low-density lipoprotein cholesterol concentrations to reduce cardiovascular events.
However, there is need for the development of early-risk assessment tools to identify individuals at high disease risk to improve long-term health outcomes. Recent genetic studies associated CD36, a protein that functions in the utilization of dietary fats, with the risk of stroke. In previous studies, we identified common variations in the CD36 gene that associated with increased fasting blood lipid concentrations and with risk for metabolic syndrome (MetS).
