Apolipoprotein C-III, n-3 polyunsaturated fatty acids, and "insulin-resistant" T-455C APOC3 gene polymorphism in heart disease patients: example of gene-diet interaction.
BACKGROUND
Apolipoprotein C-III (apo C-III) is a marker of cardiovascular disease risk associated with triglyceride (TG)-rich lipoproteins. The T-455C polymorphism in the insulin-responsive element of the APOC3 gene influences TG and apo C-III concentrations. Long-chain n-3 polyunsaturated fatty acids (PUFAs) contained in fish have well-known apo C-III-lowering properties.


METHODS
We investigated the possibility of an interactive effect between the APOC3 gene variant and erythrocyte n-3 PUFAs, suitable markers of dietary intake of fatty acids, on apo C-III concentrations in a population of 848 heart disease patients who had coronary angiography.


RESULTS
In the population as a whole, apo C-III concentrations were significantly inversely correlated with total erythrocyte PUFAs, but the correlation was not significant when only -455CC homozygous individuals were taken into account. In the total population and in subgroups with the -455TT and -455CT genotypes, the relative proportions of individuals presenting with increased apo C-III (i.e., above the 75th percentile value calculated on the entire population after exclusion of individuals taking lipids-lowering medications) decreased progressively as the n-3 PUFA and docosahexaenoic acid concentrations increased. The opposite situation was observed in the homozygous -455CC subgroup, in whom increasing erythrocyte n-3 PUFA and docosahexaenoic acid concentrations were associated with higher proportions of individuals with high apo C-III. A formal interactive effect between genotype and n-3 PUFAs was confirmed even after adjustment for possible confounding variables [age, sex, body mass index, smoking, coronary artery disease (CAD)/CAD-free status, or use of lipid-lowering medications] by logistic models.


CONCLUSIONS
Patients homozygous for the -455C APOC3 variant are poorly responsive to the apo C-III-lowering effects of n-3 PUFAs.
Olivieri
Oliviero
O
Unit of Internal Medicine, Department of Clinical and Experimental Medicine, University of Verona, Verona, Italy. oliviero.olivieri@univr.it
Martinelli
Nicola
N
Sandri
Marco
M
Bassi
Antonella
A
Guarini
Patrizia
P
Trabetti
Elisabetta
E
Pizzolo
Francesca
F
Girelli
Domenico
D
Friso
Simonetta
S
Pignatti
Pier Franco
PF
Corrocher
Roberto
R
D053305:Apolipoprotein C-III; D001056:Apolipoproteins C / Q000235:genetics*; D004042:Dietary Fats, Unsaturated; D015525:Fatty Acids, Omega-3; D005231:Fatty Acids, Unsaturated / Q000008:administration & dosage*; D005260:Female; D006331:Heart Diseases / Q000235:genetics*; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020218:Response Elements; D014280:Triglycerides / Q000008:administration & dosage*
D053305:Apolipoprotein C-III; D001056:Apolipoproteins C; D004042:Dietary Fats, Unsaturated; D015525:Fatty Acids, Omega-3; D005231:Fatty Acids, Unsaturated; D014280:Triglycerides; C077446:Pikasol