Association of apolipoprotein A-V concentration with apolipoprotein A5 gene -1131T>C polymorphism and fasting triglyceride levels

Background and Objective: The relationship between the apolipoprotein A5 gene (APOA5) -1131T>C polymorphism and triglyceride levels is well established, but the association between circulating apolipoprotein A-V (apoA-V) concentrations and APOA5 -1131T>C genotypes and triglyceride levels remains controversial. Methods: Normotriglyceridemic controls (n = 1526) and hypertriglyceridemic cases (n = 744) were genotyped for APOA5-1131T>C. ApoA-V, triglycerides, insulin, free fatty acids, and lipoprotein profiles were analyzed. Results: APOA5-1131C minor allele frequency was significantly greater in hypertriglyceridemic patients than normotriglyceridemic controls. ApoA-V concentrations were not significantly different between controls and cases. Normotriglyceridemic controls with T/C and C/C showed lower apoA-V concentrations (14% and 27%, respectively), than did T/T controls. Similar genotypic effects on apoA-V were found in hypertriglyceridemic cases. In both groups, APOA5-1131T>C was associated with higher triglycerides, smaller LDL particle size, and lower HDL-cholesterol. We observed a negative correlation between apoA-V and triglyceride in controls and a positive correlation in hypertriglyceridemic patients, regardless of genotype. We observed a positive correlation between apoA-V and free fatty acids in both groups, regardless of genotype, and a positive correlation between apoA-V and HDL-cholesterol in controls (T/T, T/C, or C/C) and hypertriglyceridemic patients (T/T or T/C). Conclusion: APOA5-1131C may lead to reduced apoA-V with concomitantly reduced lipoprotein lipase activation, resulting in greater serum triglycerides, although the correlation between apoA-V and triglyceride was reversed when triglyceride was greater than 150 mg/dL.