Apolipoprotein C-III (apoC-III), a small proinflammatory protein present on 6% to 7% of high-density lipoprotein (HDL) particles, defines a subspecies of HDL adversely associated with coronary heart disease in primarily white cohorts.
Relationship of lipoprotein-associated apolipoprotein C-III with lipid variables and coronary artery disease risk: The EPIC-Norfolk prospective population study.
Within the apolipoprotein A-I-C-III-A-IV gene cluster, the Ssti polymorphism in the 3' untranslated region of the apolipoprotein C-III gene is the variant site most consistently and strongly associated with raised plasma triglyceride levels and coronary artery disease.
The multivariate model included 512 men with coronary artery disease from the REGRESS study who were completely genotyped for eight polymorphisms selected in the univariate procedure (ie, APOA1 G(-75)A, ABCA1 C(-477)T, ABCA1 G1051A, APOC3T3206G, APOE Arg158Cys, LIPC C(-514)T, LPL Asn291Ser and LPL Ser447Stop).
Synergistic effects of the apolipoprotein E epsilon3/epsilon2/epsilon4, the cholesteryl ester transfer protein TaqIB, and the apolipoprotein C3 -482 C>T polymorphisms on their association with coronary artery disease.
We identified the haplotype S2/C with a significant increased risk (P < 0.001) to coronary artery disease with increased levels of circulating triglycerides compared to other haplotypes in patients.
The -1131 T>C and S19W APOA5 gene polymorphisms are associated with high levels of triglycerides and apolipoprotein C-III, but not with coronary artery disease: an angiographic study.
A rare variant in APOC3(rs138326449) has been associated with triglyceride, very low-density lipoprotein, and high-density lipoprotein levels, as well as risk of coronary heart disease.
Association of the Sst-I polymorphism at the APOC3 gene locus with variations in lipid levels, lipoprotein subclass profiles and coronary heart disease risk: the Framingham offspring study.
Therefore, VLDL particles with apoC-III may play a central role in identifying the high risk of coronary heart disease in hypertriglyceridemia, but their substantial prevalence in normolipidemics may be of clinical significance as well.
These impactful mouse studies were supported by the initial finding that APOC3 predicted coronary artery disease events in participants of the prospective Coronary Artery Calcification in Type 1 Diabetes study with normal TG levels.
In humans, loss-of-function mutations in APOC3 are associated with reduced plasma TG levels and reduced risk for ischemic vascular disease and coronary heart disease.