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Am J Clin Nutr. 2002 Jan;75(1):38-46.

Polyunsaturated fatty acids modulate the effects of the APOA1 G-A polymorphism on HDL-cholesterol concentrations in a sex-specific manner: the Framingham Study.

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Nutrition and Genomics Laboratory, the Lipid Metabolism Laboratory and the Epidemiology Program, Jean Mayer-US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston 02111, USA.



A common G-to-A substitution in the promoter area (-75 base pairs) of the apolipoprotein A-I gene (APOA1) has been described. The A allele was shown to be associated with higher HDL-cholesterol concentrations in some studies but not in others.


We examined whether dietary fat modulates the association between this polymorphism and HDL-cholesterol concentrations.


We studied a population-based sample of 755 men and 822 women from the Framingham Offspring Study.


The frequency of the A allele was 0.165. No significant differences were observed between G/G subjects and carriers of the A allele for any lipid variables. In multivariate linear regression models, HDL-cholesterol concentrations in women were associated with a significant interaction between polyunsaturated fatty acid (PUFA) intake as a continuous variable and APOA1 genotype (P = 0.005). By using 3 categories of PUFA intake, we found a significantly different effect of APOA1 genotype across PUFA categories in women. When PUFA intake was <4% of energy, G/G subjects had approximately 14% higher HDL-cholesterol concentrations than did carriers of the A allele (P < 0.05). Conversely, when PUFA intake was >8%, HDL-cholesterol concentrations in carriers of the A allele were 13% higher than those of G/G subjects (P < 0.05). No significant allelic difference was observed for subjects in the range of PUFA intake of 4-8% of energy. These interactions were not significant in men.


We found a significant gene-diet interaction associated with the APOA1 G-A polymorphism. In women carriers of the A allele, higher PUFA intakes were associated with higher HDL-cholesterol concentrations, whereas the opposite effect was observed in G/G women.

[Indexed for MEDLINE]

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