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.
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.
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.
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.
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 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.
Furthermore, identification of rare loss-of-function variants in genes such as PCSK9, NPC1L1, APOC3 and APOA5, which cause a markedly decreased risk of CHD and no adverse side effects, illustrates the power of translating genetic findings into novel mechanistic information and provides some optimism for the future of developing novel drugs, given the many genes associated with CHD in GWASs.
Two new studies report that triglyceride (TG)-lowering mutations in APOC3 reduce coronary heart disease (CHD) (Crosby et al., 2014; Jørgensen et al., 2014).
PubMed, EMBASE and Cochrane library databases (up to March 2013) were systematically searched to identify studies evaluating the association between ApoC3 polymorphisms and CHD risk.
Lower concentrations of apoC-III and LDL with apoC-III are associated with reduced risk of coronary heart disease (CHD) in epidemiologic studies independent of traditional risk factors.