Dietary intake of n-6 fatty acids modulates effect of apolipoprotein A5 gene on plasma fasting triglycerides, remnant lipoprotein concentrations, and lipoprotein particle size - The Framingham Heart Study

Background - Apolipoprotein A5 gene (APOA5) variation is associated with plasma triglycerides (TGs). However, little is known about whether dietary fat modulates this association. Methods and Results - We investigated the interaction between APOA5 gene variation and dietary fat in determining plasma fasting TGs, remnant-like particle (RLP) concentrations, and lipoprotein particle size in 1001 men and 1147 women who were Framingham Heart Study participants. Polymorphisms -1131T > C and 56C > G, representing 2 independent haplotypes, were analyzed. Significant gene-diet interactions between the -1131T > C polymorphism and polyunsaturated fatty acid (PUFA) intake were found (P < 0.001) in determining fasting TGs, RLP concentrations, and particle size, but these interactions were not found for the 56C > G polymorphism. The -1131C allele was associated with higher fasting TGs and RLP concentrations (P < 0.01) in only the subjects consuming a high-PUFA diet (> 6% of total energy). No heterogeneity by sex was found. These interactions showed a dose-response effect when PUFA intake was considered as a continuous variable (P < 0.01). Similar interactions were found for the sizes of VLDL and LDL particles. Only in carriers of the -1131C allele did the size of these particles increase (VLDL) or decrease (LDL) as PUFA intake increased (P < 0.01). We further analyzed the effects of n-6 and n-3 fatty acids and found that the PUFA - APOA5 interactions were specific for dietary n-6 fatty acids. Conclusions - Higher n-6 (but not n-3) PUFA intake increased fasting TGs, RLP concentrations, and VLDL size and decreased LDL size in APOA5-1131C carriers, suggesting that n-6 PUFA-rich diets are related to a more atherogenic lipid profile in these subjects.