|Irvin, Marguerite -|
|Kabagambe, Edmond -|
|Tiwari, Hemant -|
|Straka, Robert -|
|Tsai, Michael -|
|Ordovas, Jose -|
|Arnett, Donna -|
Submitted to: Circulation: Cardiovascular Genetics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: July 1, 2010
Publication Date: October 1, 2010
Citation: Irvin, M.R., Kabagambe, E.K., Tiwari, H.K., Parnell, L.D., Straka, R.J., Tsai, M., Ordovas, J.M., Arnett, D.K. 2010. Apolipoprotein E polymorphisms and postprandial triglyceridemia before and after fenofibrate treatment in the Genetics of Lipid Lowering and Diet Network (GOLDN) Study. Circulation: Cardiovascular Genetics. 3(5):462-467. Interpretive Summary: While much is known about the effects of genetic variants of Apolipoprotein E (APOE) on Alzheimer disease and levels of lipids in the blood after fasting, less is known about these genetic variants with respect to the after-meal response of triglycerides or the triglyceride response to lipid-lowering drugs. We evaluated the effects of APOE variants on fasting and after-meal triglyceride concentrations as part of the Genetics of Lipid Lowering and Diet Network (GOLDN) study, a constituent of the National Heart Blood and Lung Institute’s Family Heart Study. We found that certain genetic variants are indeed important determinants of blood triglyceride levels, especially in the fasting state. This result is important because it provides further evidence that common genetic differences can be used to partition patients into those who are at higher risk of disease. In this case, these would be individuals who, carrying the epsilon-2 version of APOE, show higher levels of triglycerides in the fasting state both before and after a short trial with a lipid-lowering drug, thereby putting these persons at higher risk for heart disease.
Technical Abstract: Background: While much is known about the effect of Apolipoprotein E (APOE) alleles on fasting lipid concentrations, less is known about the effect of APOE alleles on postprandial triglyceridemia or the triglyceride response to fenofibrate. Methods and Results: We evaluated the effects of the APOE locus on fasting and postprandial triglyceride concentrations as part of the Genetics of Lipid Lowering and Diet Network (GOLDN) study. Participants were evaluated following a high-fat meal challenge before (N=1072) and after 3 weeks of daily treatment with 160 mg of fenofibrate (N=738). Mixed models adjusted for gender, age, waist circumference and family relationship were used to examine the association of the Epsilon4 carrier and Epsilon2 carrier status versus Epsilon3 homozygotes with fasting triglycerides and the area under the curve (AUC) for triglycerides during the high-fat meal challenge. Compared to the Epsilon3/Epsilon3 genotype, Epsilon2 carriers had on average higher fasting triglyceride concentrations (130.5 milligrams per decilitre vs. 109.3 milligrams per decilitre, P<0.001). After fenofibrate treatment, the APOE genotype differences persisted in the fasting state (Epsilon2 carriers: 85.1 milligrams per decilitre vs. Epsilon3/Epsilon3: 75.9 milligrams per decilitre, P<0.05). Carriers of the Epsilon4 allele had significantly higher fasting triglyceride concentrations only pre-fenofibrate (120.9 milligrams per decilitre vs. 109.3 milligrams per decilitre, P=0.008). APOE alleles did not have an effect on response to fenofibrate. Postprandial triglycerides were significantly higher for Epsilon2 carriers versus Epsilon3 homozygotes (but not Epsilon4 carriers) both before and after fenofibrate treatment (P=0.01 and P=0.005, respectively). Conclusions: APOE polymorphisms are important determinants of triglyceride concentrations, especially in the fasting state.