The APOA1-CIII-AIV gene cluster: Effects on acute and long-term lipoprotein responses to high saturated fat diets

We hypothesized that genetic variants in the APOAI-CIII-AIV gene cluster induce a more atherogenic postprandial response.; Polymorphisms of the APOC3 gene were genotyped in the promoter region (T-455C, T-625Del) and the Sst1 (C3238G) 3′ untranslated region (UTR) in 419 randomly selected subjects from Puriscal, Costa Rica. Dietary intake was assessed by a validated food frequency questionnaire. Significant gene-diet interactions were found for total cholesterol (p < 0.0004) and LDL cholesterol (p < 0.01). In subjects homozygous for the APOC3-455T-625T allele, saturated fat intake was associated with 13–20% higher total cholesterol, LDL cholesterol (p < 0.001), apoB levels (p < 0.05) and a 1.0% increase in LDL size (p < 0.05). No association was found among carriers of the APOC3-455C-625del allele. The APOC3-455T-625T allele, but not in the Sst1 3′ untranslated region, modulated the interaction between saturated fat intake, plasma lipoproteins and LDL particle size.; Carriers of the APOAI and not the APOAIV variant modulated fasting and postprandial metabolism. In this study, 24 carriers of the APOAIV360His variant allele were matched with 24 APOAIV360Gln homozygotes. Fasting and postprandial blood samples were taken every two hours for 10 hours following a high fat meal (70% fat). PCR products were digested with restriction endonuclease enzyme Pvull for APOAIV and Msp1 for APOA1. All study subjects were 3/3 for APOE. Lipoproteins analyzed were light VLDL, dense VLDL and light LDL. No APOAIV360His gene effect was observed for triglycerides (p = 0.28), apoB (p = 0.99), and apoC3 (p = 0.19) in whole plasma and the three lipoprotein fractions. Carriers of the APOAIV360His variant allele had similar postprandial triglycerides compared to Gln/Gln homozygotes. At baseline, carriers of the APOA1-75A variant allele had higher (p ≤ 0.05) triglyceride, cholesterol, apoB and apoC3 concentrations in light VLDL and lower (p = 0.03) HDL-C concentrations in whole plasma compared to G/G subjects. Significant APOA1-75 gene effects were observed postprandially in whole plasma and the three lipoprotein fractions (p ≤ 0.05). Compared to G/G homozygotes, carriers of the A allele had postprandial triglyceride, apoB and apoC3 concentrations that were higher (p ≤ 0.05) by 30%, 15%, 35% respectively in plasma and light VLDL.