Apolipoprotein E Polymorphisms and Postprandial Triglyceridemia Before and After Fenofibrate Treatment in the Genetics of Lipid Lowering and Diet Network (GOLDN) Study

Background-Although 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 after 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 sex, age, waist circumference, and family relationship were used to examine the association of the epsilon 4 carrier and epsilon 2 carrier status versus epsilon 3 homozygotes with fasting triglycerides and the area under the curve (AUC) for triglycerides during the high-fat meal challenge. Compared with the epsilon 3/epsilon 3 genotype, epsilon 2 carriers had on average higher fasting triglyceride concentrations (130.5 mg/dL versus 109.3 mg/dL, P<0.001). After fenofibrate treatment, the APOE genotype differences persisted in the fasting state (epsilon 2 carriers: 85.1 mg/dL versus epsilon 3/epsilon 3: 75.9 mg/dL, P<0.05). Carriers of the epsilon 4 allele had significantly higher fasting triglyceride concentrations only prefenofibrate (120.9 mg/dL versus 109.3 mg/dL, P=0.008). APOE alleles did not have an effect on response to fenofibrate. Postprandial triglycerides were significantly higher for epsilon 2 carriers versus epsilon 3 homozygotes (but not epsilon 4 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. (Circ Cardiovasc Genet. 2010;3:462-467.)