The -1131T→C polymorphism in the apolipoprotein A5 gene is associated with postprandial hypertriacylglycerolemia; elevated small, dense LDL concentrations; and oxidative stress in nonobese Korean men

Abstract

Background: Apolipoprotein A5 plays an important role in modulating triacylglycerol metabolism in experimental animal models. Objective: The objective was to determine associations of the common apolipoprotein A5 gene (APOA 5) -1131T→C polymorphism with postprandial lipemic response and other cardiovascular disease risk factors in humans. Design: Healthy, nonobese subjects [n = 158; mean (±SEM) age: 33.8 ± 1.2 y; body mass index (in kg/m2): 23.3 ± 0.3] were subdivided into 3 genotype groups: TT (n = 85), TC (n = 56), and CC (n = 17). We measured fasting and postprandial lipid concentrations, lipid peroxidation, C-reactive protein concentrations, and DNA damage. Results: Fasting triacylglycerol concentrations in carriers of the C allele were higher (P < 0.05) than in carriers of the TT genotype. No other significant genotype-related differences were observed for any of the other baseline measures. After consumption of a mixed meal, carriers of the C allele had significantly greater increases in total chylomicron and VLDL triacylglycerol than did subjects with the TT genotype. Moreover, carriers of the C allele had higher dense LDL, serum C-reactive protein, and urinary 8-epi-prostaglandin F2α concentrations and more lymphocyte DNA damage. Conversely, we did not find significant genotype-related differences in postprandial glucose, insulin, or free fatty acid measures. Conclusions: Our data confirm the genetic modulation of serum fasting triacylglycerol concentrations by the APOA5 gene polymorphism and extend this observation to postprandial triacylglycerol concentrations and to markers of oxidation and inflammation. The presence of the C allele in the APOA5 promoter region at position 1131 could be a significant factor contributing to higher cardiovascular disease risk in Koreans independently of common environmental factors. © 2004 American Society for Clinical Nutrition.