Published Online
on April 24, 2006

A more recent version of this article appeared on May 2, 2006

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Submitted on July 20, 2005
Revised on February 17, 2006
Accepted on February 23, 2006

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

Chao-Qiang Lai PhD^*, Dolores Corella PhD, Serkalem Demissie PhD, L. Adrienne Cupples PhD, Xian Adiconis MSc, Yueping Zhu MSc, Laurence D. Parnell PhD, Katherine L. Tucker PhD, and Jose M. Ordovas PhD

From the Nutrition and Genomics Laboratory (C-Q.L., D.C., X.A., Y.Z., L.D.P., J.M.O.) and the Dietary Assessment and Epidemiology Research Program (K.L.T.), JM-USDA Human Nutrition Research Center on Aging, Tufts University, Boston, Mass; the Genetic and Molecular Epidemiology Unit (D.C.), School of Medicine, University of Valencia, Valencia, Spain; and the School of Public Health (S.D., L.A.C.), Boston University, Boston, Mass.

^* To whom correspondence should be addressed. E-mail: chao.lai{at}tufts.edu.

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.

Key words: diet • fatty acids • genetics • lipids • lipoproteins

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