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RECENT PUBLICATIONS ON RESIDUAL RISK

2017

Missense APOC3 variant lowers plasma triglycerides

APOC3 encodes apolipoprotein (apo) C-III, a critical inhibitor of triglyceride lipolysis and remnant triglyceride rich lipoprotein clearance. Genetic studies have investigated the association between APOC3 variants and risk for ischaemic heart disease, paving the way for new therapeutic approaches to managing elevated triglycerides.
 
This report details the mechanism of lowering of triglyceride-rich lipoproteins by the APOC3 Ala43Thr (A43T) variant, the only missense variant in APOC3 reported to lower triglycerides and protect against ischaemic heart disease. In mice expressing human APOC3 A43T, marked reduction in plasma apoC-III levels was due to impaired binding of A43T apoC-III to lipoproteins and accelerated catabolism of free apoC-III, as well as accelerated clearance of circulating triglyceride-rich lipoproteins. These findings have been the driver for the development of new therapeutic approaches to reduce apoC-III levels and the burden of triglyceride-rich lipoproteins.
A human APOC3 missense variant and monoclonal antibody accelerate apoC-III clearance and lower triglyceride-rich lipoprotein levels.

Khetarpal SA, Zeng X, Millar JS et al.