ARS | Publication request: Two independent apolipoprotein A5 haplotypes modulate postprandial lipoprotein metabolism in a healthy Caucasian population

Submitted to: Journal of Clinical Endocrinology and Metabolism
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: March 1, 2007
Publication Date: March 13, 2007
Publisher's URL: http://jcem.endojournals.org/cgi/content/abstract/92/6/2280
Citation: Moreno, R., Perez-Jimenez, F., Marin, C., Perez-Martinez, P., Gomez, P., Jimenez-Gomez, Y., Delgado-Lista, J., Moreno, J.A., Tanaka, T., Ordovas, J.M., Lopez-Miranda, J. 2007. Two independent apolipoprotein A5 haplotypes modulate postprandial lipoprotein metabolism in a healthy Caucasian population. Journal of Clinical Endocrinology and Metabolism. 92(6):2280-85.

Interpretive Summary: Most of diurnal time is spent in a postprandial state due to successive meal intakes along the day. Several lines of evidence suggest that postprandial lipemia increases the risk of atherogenesis and the roles of many genes have been explored in order to establish the possible implications of their variability in coronary heart risk. Recently a gene that codes for apolipoprotein A5 (APOA5) has been identified on human chromosome 11. APOA5 plays an important role in plasma lipids homeostasis. We have investigated the relation between blood lipids following the consumption of a fat meal and the apoA5 variants in the APOA5 gene. In summary, our data show that this mutation modulates the response to fat intake and this information can be used to provide more personalized dietary recommendations to prevent heart disease.

Technical Abstract: 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, 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/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 hours until the 11(th) hour. Total plasma cholesterol (C) and TG, and C, TG, Apo B-100, Apo B-48, and retinyl palmitate (RP) 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 triacylglycerol-rich lipoproteins (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 apoB100 (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 are associated with a higher postprandial response which could be involved in the higher risk of CHD associated with the 56G and -1131C alleles.