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.
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The Apo CIII reduction with OM3-FFA is consistent with prior findings of reduced Apo CIII after EPA plus DHA ingestion.
“This is consistent with prior findings of reduced Apo CIII after ingestion of EPA 1 DHA.”
From Omega-3 free fatty acids for the treatment of severe hypertriglyceridemia: The EpanoVa fOr Lowering Very high triglyceridEs (EVOLVE) trial (2014) · cites this paper as [48]
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- Authors
- Olivieri, O., Martinelli, N., Sandri, M., Bassi, A., Guarini, P., Trabetti, E., Pizzolo, F., Girelli, D., Friso, S., Pignatti, P. F., & Corrocher, R.
- Affiliations
- Unit of Internal Medicine, Department of Clinical and Experimental Medicine,
- Institute of Clinical Chemistry, and
- University of Verona (IT)
- Corresponding author
- Olivieri, Oliviero
- ORCID
- Venue
- Clinical Chemistry
- Publisher
- Oxford University Press (OUP)
- Published
- 2005-02-01
- Volume
- 51
- Issue
- 2
- Pages
- 360-367
- ISSN
- 0009-9147 (ISSN-L)
- 1530-8561
- OpenAlex
- W2126467966
- Cited by
- 50
- References
- 30
- Citations by year
- 2025: 1 · 2021: 1 · 2020: 1 · 2019: 1 · 2018: 1 · 2017: 2 · 2016: 1 · 2015: 4 · 2014: 4 · 2013: 4 · 2012: 3
- FWCI
- 3.01
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Clinical Chemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Regione del Veneto
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Nutrition, Genetics, and Disease
- Keywords
- apolipoprotein C-III, omega-3 fatty acids, docosahexaenoic acid, gene-diet interaction, triglyceride-rich lipoproteins, coronary artery disease, erythrocyte fatty acids, triglyceride metabolism
- MeSH terms
- Apolipoproteins C, Dietary Fats, Unsaturated, Fatty Acids, Unsaturated, Female, Heart Diseases, Humans, Insulin Resistance, Male, Middle Aged, Polymorphism, Genetic, Triglycerides, Fatty Acids, Omega-3, Response Elements, Apolipoprotein C-III
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