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(Circulation. 2006;113:2062-2070.)
© 2006 American Heart Association, Inc.

Epidemiology

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; 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.

Correspondence to Dr C.-Q. Lai, Nutrition and Genomics Laboratory, JM-USDA-HNRCA, Tufts University, 711 Washington St, Boston, MA 02111. E-mail chao.lai{at}tufts.edu

Received July 20, 2005; revision received February 17, 2006; accepted February 23, 2006.

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.

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