DNA HealthLipid Metabolism

Apolipoprotein C3

APOC3 C3175G

Allele frequency in population:

According to the 1000 Genomes database, the minor G allele has a frequency of 23% in the general population.

Gene and SNP Summary 

APOC3 is a protein that plays an important role in lipid metabolism. It inhibits lipoprotein lipase and hepatic lipase, two enzymes responsible for fat catabolism. A positive correlation has been observed between raised plasma APOC3 levels and elevated levels of plasma triglycerides, indicating that APOC3 can be a relevant predictor of dietary low-density lipoprotein cholesterol (LDL-C) response. Carriers of the G allele have consistently been shown to have higher circulating levels of APOC3 and hence raised plasma triglyceride (TG) levels. Delayed clearance of triglyceride-rich lipoproteins results in hypertriglyceridemia, a disorder that is a strong contributing factor for atherosclerosis and myocardial infarction. Carriers of the G variant have an approximately 4-fold increased risk of hypertriglyceridemia.




APOC3 Gene Detail

The APOC3 gene encodes apolipoprotein C3, a protein component of triglyceride (TG)-rich lipoproteins. APOC3 plays a multifaceted role in triglyceride homeostasis where it has been shown to promote the assembly and secretion of VLDL, inhibit lipoprotein lipase and hepatic lipase enzyme activity, and delay catabolism of triglyceride-rich lipoproteins remnants. 


Raised APOC3 levels are linked to increased predisposition to hypertriglyceridemia and risk for atherosclerosis.



APOC3 C3175G

The APOC3 C3175G SNP has been associated with metabolic syndrome, CVD and type 2 diabetes. The APOC3 GG genotype is linked to increased levels of APOC3 in plasma, and thus increased risk for hypertriglyceridemia, CVD and metabolic syndrome. A recent meta-analysis confirmed the relationship between the G allele and increased odds for having raised APOC3 levels as well as higher TG, TC and LDL-C. 


Interestingly, a review of the evidence showed that CC genotype individuals may experience negative phenotype effects in combination with certain unhealthy lifestyle exposures. In CC genotype carriers, a diet high in fast food was associated with increased risk of metabolic syndrome. Also, a diet high in saturated fat was linked to higher LDL-C in C allele carriers compared to GG genotype individuals.




Despite the risk factors associated with the G allele, carriers of the CG and GG genotype also show greatest responsiveness to altered dietary fat intake, where a diet high in monounsaturated fatty acids (MUFA) lead to a greater decrease in LDL-C compared to C allele carriers. Their increased risk of cardiovascular disease is thus modifiable by regulation of the amount and type of fat consumed. Carriers of the G variant may also show enhanced benefit to statin therapy.

It is important to note that CC genotype carriers may respond with adverse effects to a diet high in saturated fat and fast foods, and recommendations to keep to a low saturated fat diet and avoid fast food intake would be beneficial.




Associations of the APOC3 rs5128 polymorphism with plasma APOC3 and lipid levels: a meta-analysis

Song et al, 2015.