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Two Independent Apolipoprotein A5 Haplotypes Modulate Postprandial Lipoprotein Metabolism in a Healthy Caucasian Population

Unit of Lipids and Atherosclerosis (R.M.-L., F.P.-J., C.M., P.P.-M., P.G., Y.J.-G., J.D.-L., J.A.M., J.L.-M.), Hospital Universitario Reina Sofia, 14004 Cordoba, Spain; and Nutrition and Genomics Laboratory (T.T., J.M.O.), U.S. Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts 02111-1524

Address all correspondence and requests for reprints to: Professor Jose Lopez-Miranda, Unidad de Lípidos y Arteriosclerosis, Hospital Universitario Reina Sofía, Avda Menéndez Pidal, s/n. 14004 Córdoba, Spain. E-mail: jlopezmir{at}uco.es.

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.