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.

Abstract

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.

CONCLUSION:

Patients homozygous for the -455C APOC3 variant are poorly responsive to the apo C-III-lowering effects of n-3 PUFAs.

• Authors: Oliviero Olivieri, Nicola Martinelli, Marco Sandri, Antonella Bassi, Patrizia Guarini, Elisabetta Trabetti, Francesca Pizzolo, Domenico Girelli, Simonetta Friso, Pier Franco Pignatti, Roberto Corrocher
• Journal: Clinical chemistry (Clin Chem) Vol. 51 Issue 2 Pg. 360-7 (Feb 2005) ISSN: 0009-9147 [Print] England
• PMID: 15576429 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Apolipoprotein C-III
• Apolipoproteins C
• Dietary Fats, Unsaturated
• Fatty Acids, Omega-3
• Fatty Acids, Unsaturated
• Triglycerides
• Pikasol

Topics

• Apolipoprotein C-III
• Apolipoproteins C (genetics)
• Dietary Fats, Unsaturated
• Fatty Acids, Omega-3
• Fatty Acids, Unsaturated (administration & dosage)
• Female
• Heart Diseases (genetics)
• Humans
• Insulin Resistance (genetics)
• Male
• Middle Aged
• Polymorphism, Genetic
• Response Elements
• Triglycerides (administration & dosage)