Abstract 18754: Genetic Predisposition to Coronary Artery Disease and Changes in Lipid Profile in Response to 2-year Weight-loss Diet Intervention: The Pounds Lost Trial

Abstract

Introduction: Dyslipidemia is a major risk factor of coronary artery disease (CAD), and is affected by interaction between genetic and environmental factors, such as diets. Weight-loss diet intervention has been widely used to improve lipids to mitigate cardiovascular complications of obesity. Hypothesis: We hypothesize that the genetic predisposition to CAD may modify lipids metabolism in response to diets. Methods: We calculated a genetic risk score (GRS) based on 19 CAD-associated single nucleotide polymorphisms in 744 adults from a 2-year diet intervention study: the POUNDS Lost trial. We examined the changes in total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol and triglycerides by the GRS and diet intervention. Results and Conclusions: We found significant interaction between the GRS and dietary fat intake on changes in total cholesterol, HDL and LDL cholesterol (P-interaction=0.02, 0.01 and 0.02, respectively) after the 2-year intervention. Overall, both low- and high-fat diets decreased total cholesterol, LDL cholesterol and triglycerides, but increased HDL cholesterol. At 2 years, in the highest tertile of the GRS, participants eating the low-fat diet showed a greater decrease in total cholesterol and LDL cholesterol than those eating the high-fat diet; whereas participants eating the high-fat diet showed a greater increase in HDL cholesterol than those eating the low-fat diet (all P<0.001). In lower tertiles of the GRS, the difference in lipids changes between the two diet groups was not significant. In conclusion, genetic predisposition to CAD might modify the dietary fat induced lipids changes. Our data suggest that in participants with higher genetic risk, low-fat diet may lower total cholesterol and LDL cholesterol, while high-fat diet may improve HDL cholesterol. And in participants with lower genetic risk, the two diets showed similar effects on improvement of lipid profile.