Abstract 4168: Two Independent Apolipoprotein A5 Haplotypes Modulate Postprandial Lipoprotein Metabolism in a Caucasian Healthy Population.

Abstract

Background: APOA5 plays an important role in plasma plasma triglyceride (TG) homeostasis. Five polymorphisms (1131T>C, c.-3A>G, c.56C>G, IVS3+476G>A, c.1259T>C) in the APOA5 gene were found to define three common haplotypes (denoted 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, in order to explain the higher risk of coronary artery disease (CHD) associated with less common alleles Design and methods: 84 apo E3E3 volunteers [63 with (-1131T and 56C) haplotype 1, 12 with (-1131C and 56C) haplotype 2 and 9 with (-1131T and 56G) haplotype 3] underwent a fat-load test consisting of 1 g of fat/kg body weight and 60,000 IU of vitamin A. Blood samples were taken at time 0 and every hour until the 6 th and every 2.5 hr until the 11 th . Cholesterol (Chol) and TG were determined in plasma and Chol, TG, Apo B-100, Apo B-48, and retinyl palmitate (RP) were determined in lipoprotein fractions. Results: Data of postprandial lipemia revealed that subjects with the haplotypes 2 and 3 had a higher area under the curve than subjects with the haplotype 1 of total plasma TG (0.28±0.1 and 0.31±0.1 vs 0.21±0.1 mmol/L s, p0.04), large triacylglycerol-rich lipoproteins (TRL)-TG (0.19±0.07 and 0.22±0.09 vs 0.10±0.04 mmol/L s, p=0.01), small TRL-TG (0.15±0.06 and 0.14±0.07 vs 0.9±0.05 mmol/L s, p=0.03), large TRL-Cho (0.05±0.01 and 0.06±0.01 vs 0.03±0.061 mmol/L s, p=0.04), and small apoB100 (639±315 and 219±158 vs 140±86, p=0.03). Conclusions : Our findings show that the presence of the haplotype 2 and 3 in the APO5 gene are associated with a higher postprandial response and could be involved in a higher risk of CHD.