Dietary Intake of n-6 Fatty Acids Modulates Effect of Apolipoprotein A5 Gene on Plasma Fasting Triglycerides, Remnant Lipoprotein Concentrations, and Lipoprotein Particle Size

Abstract

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 Ϫ1131TϾC and 56CϾG, representing 2 independent haplotypes, were analyzed. Significant gene-diet interactions between the Ϫ1131TϾC polymorphism and polyunsaturated fatty acid (PUFA) intake were found (PϽ0.001) in determining fasting TGs, RLP concentrations, and particle size, but these interactions were not found for the 56CϾG polymorphism. The Ϫ1131C allele was associated with higher fasting TGs and RLP concentrations (PϽ0.01) in only the subjects consuming a high-PUFA diet (Ͼ6% 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 (PϽ0.01). Similar interactions were found for the sizes of VLDL and LDL particles. Only in carriers of the Ϫ1131C allele did the size of these particles increase (VLDL) or decrease (LDL) as PUFA intake increased (PϽ0.01). 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 Ϫ1131C carriers, suggesting that n-6 PUFA-rich diets are related to a more atherogenic lipid profile in these subjects.

Nutrigenomics: interaction between certain genetic polymorphisms and a diet

“…Apolipoprotein A5 (Apo A5) pomembno uravnava presnovo lipoproteinov, bogatih s trigliceridi (TG) (38). Apo A5 ima dve vlogi: sodeluje pri tvorbi lipoproteinov zelo majhne gostote (VLDL) (39), poleg tega pa pospe{i hidrolizo TG, in sicer aktivira lipoprotein lipazo (40). Razli~ni polimorfizmi v genu APOA5 so povezani s pove~ano koncentracijo TG in delcev VLDL v plazmi (41).…”

“…Razli~ni polimorfizmi v genu APOA5 so povezani s pove~ano koncentracijo TG in delcev VLDL v plazmi (41). Naknadno pa so predpostavili, da na povezavo med genom APOA5 in ravnijo ma{~ob v krvi vpliva prav vnos dolo~enega tipa ma{~ob (40). Hipotezo o vnosu ma{~obnih kislin, ki razli~no vplivajo na presnovo ma{~ob pri posameznikih z razli~nimi polimorfizmi v genu APOA5, so potrdili na populaciji, ki jo je zajemala Framinghamova {tudija (37).…”

Nutrigenetics and personalised nutrition: how far have we progressed and are we likely to get there?

“…An analysis of data from the Framingham cohort indicates that the association is modulated by dietary PUFA composition (102) . Fish oil fatty acids are the most potent known dietary hypotriacylglycerolaemic agents, with 20-40 % reduction typically observed following high-dose intakes (2-4 g EPA + DHA/d) (72) .…”

Nutrigenomics: a case for the common soil between cardiovascular disease and cancer

“…Several common APOA5 SNPs have been associated with increased plasma total TG, RLP, and VLDL concentrations [27,28,43]. However, the association between APOA5 gene and postprandial lipid levels was suggested to be modulated by the type of fat consumed with the diet [20,34].…”

“…In particular, the hypothesis that FA intake may modulate the effect of APOA5 variants on lipid metabolism was assessed in the Framingham population by Lai et al [27], who examined the interaction between the APOA5-1131T[C and 56C[G polymorphisms and FA intake in their relation to the body mass index (BMI) and obesity risk in men and women. They found a consistent and statistically significant interaction between the -1131T[C SNP (but not the 56C[G) and total fat intake for BMI.…”