ABCA1 gene variants regulate posprandial lipid metabolism in healthy men

Authors: DELGADO-LISTA, JAVIER - Universidad De Cordoba; PEREZ-MARTINEZ, PABLO - Universidad De Cordoba; PEREZ-JIMINEZ, FRANCISCO - Universidad De Cordoba; GARCIA-RIOS, ANTONIO - Universidad De Cordoba; FUENTES, FRANCISCO - Universidad De Cordoba; MARIN, CARMEN - Universidad De Cordoba; GOMEZ-LUNA, PURIFICACION - Universidad De Cordoba; CAMARGO, ANTONIO - Universidad De Cordoba; Parnell, Laurence; ORDOVAS, JOSE - Tufts University; LOPEZ-MIRANDA, JOSE - Universidad De Cordoba

Submitted to: Arteriosclerosis Thrombosis and Vascular Biology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/10/2010
Publication Date: 5/1/2010
Citation: Delgado-Lista, J., Perez-Martinez, P., Perez-Jiminez, F., Garcia-Rios, A., Fuentes, F., Marin, C., Gomez-Luna, P., Camargo, A., Parnell, L.D., Ordovas, J.M., Lopez-Miranda, J. 2010. ABCA1 gene variants regulate posprandial lipid metabolism in healthy men. Arteriosclerosis Thrombosis and Vascular Biology. 30(5):1051-1057.

Interpretive Summary: Genetic variants of ABCA1, a member of a large family of conserved transmembrane proteins, have been linked to both altered progression of the atherosclerosis condition and differences in blood lipid (fat) levels after overnight fasting, particularly HDL (“good” cholesterol) and a component known as apolipoprotein A (APOA1). However, results from many studies have been inconsistent. In order to further characterize the effects of genetic variants of ABCA1 in fat biochemistry after meals in humans, we studied the influence of three genetic variants during the after-meal rise of blood lipid levels in 88 normal young men, who were challenged with a high-fat meal. For two of the genetic variants, both fasting and after-meal values of APOA1 were higher, and the after-meal blood lipid response was much lower in persons carrying the common version of the variants. These persons also showed higher APOA1/APOB ratio, a measure of blood lipid health. One of these genetic variants with the third variant showed additionally higher levels of HDL-cholesterol after overnight fast and lower after-meal levels of APOB, both aspects of a healthier blood lipid profile. Our work shows that persons harboring the less common versions of two specific variants of the ABCA1 gene have elevated after-meal responses of certain blood lipids than do the persons with two copies of the common version. This finding may further characterize the role of ABCA1 in lipid biochemistry and can identify persons at increased risk of cardiovascular disease, as a consequence of elevated levels of triglycerides during the after-meal period.

Technical Abstract: Objective: Genetic variants of ABCA1, a member of a large family of conserved transmembrane proteins, have been linked to altered atherosclerosis progression and fasting lipid concentration, mainly HDL and Apolipoprotein A, but results from different studies have been inconsistent. Methods and results: In order to further characterize the effects of ABCA1 variants in human postprandial lipid metabolism, we studied the influence of three SNPs [i27943 (rs2575875); i48168 (rs4149272); R219K (rs2230806)] in the postprandial lipemia of 88 normolipidemic young men, who were given a fatty meal. For i27943 and i48168 SNPs, fasting and postprandial values of APOA1 were higher, and postprandial lipemia was much lower in major allele homozygotes, for total triglycerides in plasma, and large-TRL triglycerides. These persons also showed higher APOA1/APOB ratio. Major allele homozygotes for i48168 and i19342 showed additionally higher fasting HDL and lower postprandial ApoB. Conclusions: Our work shows that carriers of the minor alleles for ABCA1 SNPs i27943 and i48168 have a higher postprandial response as compared to major allele homozygotes. This finding may further characterize the role of ABCA1 in lipid metabolism and can identify persons at increased risk of cardiovascular disease, as a consequence of elevated postprandial hypertriglyceridemia.