ARS | Publication request: The -1131t>c Polymorphism in the Apolipoprotein A5 (Apoa5) Gene Is Associated with Postprandial Hypertriacylglycerolemia, Elevated Small Dense Ldl Concentrations and Oxidative Stress in Non-Obese Korean Men

Submitted to: American Journal Of Clinical Nutrition
Publication Acceptance Date: April 16, 2004
Publication Date: October 1, 2004
Publisher's URL: http://www.ajcn.org/cgi/content/full/80/4/832
Citation: Jang, Y., Kim, J.Y., Kim, O.Y., Lee, J.E., Cho, H., Ordovas, J.M., Lee, J.H. 2004. The -1131t>c Polymorphism In The Apolipoprotein A5 (Apoa5) Gene Is Associated With Postprandial Hypertriacylglycerolemia, Elevated Small Dense Ldl Concentrations And Oxidative Stress In Non-Obese Korean Men. American Journal Of Clinical Nutrition. 80(4):832-840.

Interpretive Summary: Most humans in developed countries are for most of the day in a non-fasting state. The blood concentrations of lipoproteins during the postprandial phase are very different than those measured in the fasting state and they are related with risk of cardiovascular diseases. The response to food varies among individuals and this is due to several factors including age, sex and genetics. A protein known as apolipoprotein AV plays an important role in modulating triacylglycerol (TG) metabolism in experimental animal models. Our objective was to determine associations of polymorphism in this gene with postprandial response and other cardiovascular disease (CVD) risk factors in humans. Our data shows that fasting triglyceride concentrations in carriers of a mutation in the gene were higher than in those carrying the normal gene. Following consumption of a meal, carriers of the mutation had greater increase of atherogenic lipids in blood as compared with normal subjects. Moreover, carriers of the mutation had higher small, dense, low density lipoproteins as well as markers of oxidation and inflammation. The presence of the mutation at the APOA5 gene may be a significant factor to contributing to higher CVD risk.

Technical Abstract: The apolipoprotein AV plays an important role in modulating triacylglycerol (TG) metabolism in experimental animal models. Our objective was to determine associations of a common apolipoprotein A5 (APOA5) '1131T>C gene polymorphism with postprandial lipemic response and other cardiovascular disease (CVD) risk factors in humas. For this purpose, healthy non-obese subjects (n=158; age: 33.8+/-1.2 yrs; BMI 23.3+/-0.3 kg/m^2) were subdivided into 3 genotypes groupsl TT (n=85), TC (n=56) or CC (n=17). We measured fasting and postprandial lipid levels, lipid peroxidation, C-reactive protein (CRP) and DNA damage. Our data shows that fasting TG concentrations in carriers of the C allele were higher (P<0.05) than those carrying the TT genotype. No other significant genotype-related differences were observed for any of the other baseline measures. Following consumption of a mixed meal, carriers of the C allele had significantly greater increases of total chylomicron and very low density lipoprotein TG as compared with TT subjects. Moreover, carriers of the C allele had higher dense LDL, serum CRP, urinary 8-epi-prostaglandin F2-alpha concentrations and higher lymphocyte DNA damage. Conversely, we did not find significant genotype-related differences for postprandial glucose, insulin and free fatty acids measures. In conclusion, our data confirm the genetic modulation of the APOA5 gene polymorphism on serum fasting TG and extends those observations to postprandial TG concentrations and to markers of oxidation and inflammation. The presence of the C allele at the APOA5 (-1131T>C) SNP may be a significant factor contribution to higher CVD risk in Koreans independently of common environmental factors.