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.
In conclusion, our results provide evidence that the rs4225 in the 3'-UTR of APOC3 might contribute to the risk of CHD by interfering with miR-4271 binding.
More recently, whole-exome sequencing studies have revealed loss-of-function mutations in ANGPTL3 associated with pan-hypolipidemia, and in APOC3 that confer protection against CHD.
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.
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.