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


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


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


RESULTS
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.


CONCLUSIONS
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.
Ordovas
Jose M
JM
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. ordovas@hnrc.tufts.edu
Corella
Dolores
D
Cupples
L Adrienne
LA
Demissie
Serkalem
S
Kelleher
Alison
A
Coltell
Oscar
O
Wilson
Peter W F
PW
Schaefer
Ernst J
EJ
Tucker
Katherine
K
D000328:Adult; D017677:Age Distribution; D000368:Aged; D016632:Apolipoprotein A-I / Q000187:drug effects / Q000235:genetics*; D008076:Cholesterol, HDL / Q000097:blood*; D004041:Dietary Fats / Q000494:pharmacology*; D002149:Energy Intake; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011159:Population Surveillance; D017678:Sex Distribution
D016632:Apolipoprotein A-I; D008076:Cholesterol, HDL; D004041:Dietary Fats; D005231:Fatty Acids, Unsaturated