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This version published online on March 13, 2007
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2006-1802
A more recent version of this article appeared on June 1, 2007
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Submitted on August 16, 2006
Accepted on March 1, 2007

Two independent apolipoprotein A5 haplotypes modulate postprandial lipoprotein metabolism in a healthy Caucasian population

Rafael Moreno, Francisco Perez-Jimenez, Carmen Marin, Pablo Perez-Martinez, Purificacion Gomez, Yolanda Jimenez-Gomez, Javier Delgado-Lista, Juan A. Moreno, Toshiko Tanaka, Jose M. Ordovas, and Jose Lopez-Miranda*

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

* To whom correspondence should be addressed. 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, 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 6th and every 2.5 hours until the 11th 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.
Key words: APOA5 gene • postprandial lipemia • haplotypes • triacylglycerol; nutrigenetics






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