Apolipoprotein AV and Its Role in Triglyceride Metabolism

Abstract

Apolipoprotein AV (APOAV) is a recently identified member of the apolipoprotein gene family discovered through comparative sequence analysis within the APOA1/C3/A4 gene cluster. Research has shown that changes in APOAV levels significantly influence plasma triglyceride concentrations. In mice, overexpression of human APOAV reduces triglycerides while the absence of APOAV leads to a substantial increase. Human studies present mixed findings; some indicate a positive correlation between APOAV and triglyceride levels, while others show no significant relationship. Despite its low plasma concentration, ranging from 24 to 406 mg/L, APOAV profoundly impacts lipid levels, a feature distinguishing it from other major HDL apolipoproteins. Elevated APOAV levels have also been observed in patients with inflammation and coronary artery disease (CAD), although the underlying reasons remain unclear. Polymorphisms in the APOAV gene define several common haplotypes associated with significant variations in triglyceride levels across different populations. Consistent evidence from clinical studies supports the association between APOAV haplotypes and increased plasma triglyceride levels. APOAV is thus recognized as an important gene in triglyceride metabolism in both humans and mice, although its exact mechanism of action remains to be fully understood.