ARS | Publication request: An apolipoprotein A-II polymorphism (-265T/C, rs5082), regulates postprandial response to a saturated fat overload in healthy men

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: July 2, 2007
Publication Date: August 23, 2007
Citation: Delgado-Lista, J., Perez-Jimenez, F., Tanaka, T., Perez-Martinez, P., Jiminez-Gomez, Y., Marin, C., Ruano, J., Parnell, L.D., Ordovas, J.M., Lopez-Miranda, J. 2007. An apolipoprotein A-II polymorphism (-265T/C, rs5082), regulates postprandial response to a saturated fat overload in healthy men. Journal of Nutrition. 137:2024-2028.

Interpretive Summary: Apolipoprotein (Apo) A-II is an apolipoprotein with an unknown role in lipid metabolism. It has been suggested that the presence of the less frequent genetic marker in the gene-control region (Apo A-II -265T/C, rs5082) reduces APOA2 gene activity and enhances clearance of VLDL after a meal in middle-aged men. To further investigate the role of sequence variation at this important genetic marker with respect to lipid metabolism, we studied 88 young men with normal blood lipid levels. The participants were given a fatty meal containing 1 g fat and 7 mg cholesterol/kg weight and capsules containing 60,000 IU vitamin A per square meter body surface area. After-meal blood lipid levels were assessed during the 11 h following the meal. Total cholesterol and triacylglycerols (TG) in plasma and TG-rich lipoproteins (TRL) (large TRL and small TRL) were measured, as well as HDL-cholesterol. Levels in TG and TRLs (both large and small) exhibited the greatest change during this after-meal period and that change was dependent on the particular variant the subjects carried in the gene-control region of the AOPA2 gene: individuals who were TT at position -265 had levels of TG and TRL that were 21-27% higher than those who were C carriers (either TC or CC at position -265). These results indicate that individuals harboring the rarer genetic variant for Apo A-II at position -265 have a lower, healthier after-meal response compared with common TT homozygotes. This finding may partially explain the role of Apo A-II in lipid metabolism and can identify a population with a decreased risk of cardiovascular disease.

Technical Abstract: Apolipoprotein (Apo) A-II is an apolipoprotein with an unknown role in lipid metabolism. It has been suggested that the presence of the less frequent allele of a single nucleotide polymorphism (Apo A-II -265T/C, rs5082) reduces the transcription rate of Apo A-II and enhances VLDL postprandial clearance in middle-aged men. To further investigate the role of Apo A-II -265T/C on lipid metabolism, we studied 88 normolipidemic young men. The participants were given a fatty meal containing 1 g fat and 7 mg cholesterol/kg weight and capsules containing 60,000 IU vitamin A (retinyl palmitate, 15.15 mg RE) per square meter body surface area. Postprandial lipemia was assessed during the 11 h following the meal. Total cholesterol (Chol) and triacylglycerols (TG) in plasma and TG-rich lipoproteins (TRL) (large TRL and small TRL) were measured, as well as HDL, Apo A-I, Apo B, Apo B-48, and Apo B-100. Postprandial responses were higher in the TT group than in carriers of the minor allele (CC/TC) for total TG in plasma (21.37% of change of area under curve, P = 0.014), large TRL-TG (24.75% change, P = 0.017) and small TRL-Chol (26.63% change, P = 0.003). Our work shows that carriers of the minor allele for Apo A-II -265T/C (CC/TC) have a lower postprandial response compared with TT homozygotes. This finding may partially explain the role of Apo A-II in lipid metabolism and can identify a population with a decreased risk of cardiovascular disease, as corresponds to the lower level of postprandial hypertriglyceridemia.