Two independent apolipoprotein a5 haplotypes modulate postprandial lipoprotein metabolism in a healthy Caucasian population

Background: Apolipoprotein A5 (APOA5) plays an important role in plasma triacylglycerol (TG) homeostasis. Five polymorphisms (1131T > C, c.-3A > G, c. 56C > G, IVS3 + 476G > A, and c. 1259T > C) in the APOA5 gene define three common haplotypes (APOA5* 1, APOA5* 2, and APOA5* 3) in Caucasian individuals. Our aim was to determine whether these haplotypes could modulate the postprandial response in young healthy males. Design and Methods: Eighty-eight APO E3/3 volunteers [67 with (-1131T and 56C) APOA5* 1 haplotype, 12 with (-1131C and 56C) APOA5* 2 haplotype, and nine with (-1131T and 56G) APOA5* 3 haplotype] underwent a fat load test consisting of the consumption of 1 g of fat per kilogram body weight and 60,000 IU vitamin A. Blood samples were taken at time 0, at every hour until the sixth hour, and at every 2.5 h until the 11th hour. Total plasma cholesterol (C) and TG, and C, TG, apolipoprotein B-100, apolipoprotein B-48, and retinyl palmitate in lipoprotein fractions were determined. Results: Subjects with the APOA5* 2 and APOA5* 3 haplotypes had a higher area under the curve of total plasma TG (P = 0.03), large TG-rich lipoprotein (TRL)-TG (P = 0.02), small TRL-TG (P = 0.04), small TRL-C (P = 0.04), large TRL-C (P = 0.03), and small apolipoprotein B100 (P = 0.04) than subjects with the APOA5* 1 haplotype. Conclusions: Our findings show that the presence of the APOA5* 2 and APOA5* 3 haplotypes in the APOA5 gene is associated with a higher postprandial response that could be involved in the higher risk of coronary heart disease associated with the 56G and = 1131C alleles.