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

Circulation. 2006 May 2;113(17):2062-70. doi: 10.1161/CIRCULATIONAHA.105.577296. Epub 2006 Apr 24.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Aged
  • Apolipoprotein A-V
  • Apolipoproteins / genetics*
  • Apolipoproteins A
  • Cardiovascular Diseases / prevention & control
  • Cholesterol / blood*
  • Fasting
  • Fatty Acids, Omega-6 / administration & dosage*
  • Female
  • Haplotypes
  • Humans
  • Lipoproteins / blood*
  • Lipoproteins, LDL / chemistry*
  • Lipoproteins, VLDL / chemistry*
  • Male
  • Middle Aged
  • Particle Size
  • Polymorphism, Single Nucleotide*
  • Triglycerides / blood*


  • APOA5 protein, human
  • Apolipoprotein A-V
  • Apolipoproteins
  • Apolipoproteins A
  • Fatty Acids, Omega-6
  • Lipoproteins
  • Lipoproteins, LDL
  • Lipoproteins, VLDL
  • Triglycerides
  • remnant-like particle cholesterol
  • Cholesterol