GPIHBP1: A new chylomicronemia gene

Gpihbp 1-deficient mice exhibit severe chylomicronemia, even on a low-fat diet, with grossly lipemic plasma and plasma triglyceride levels as high as 5000 mg/dl. GPIHBP1 is expressed on the luminal surface of endothelial cells of heart, muscle and fat, precisely where the lipolytic processing of triglyceride-rich lipoproteins occurs. When GPIHBP1 Is expressed in cultured cells, if confers upon those cells the capacity to bind both chylomicrons and lipoprotein lipase, suggesting that GPIHBP1 is a key platform for the lipolytic processing of chylomicrons in capillaries. These cell culture and mouse studies suggested the possibility that some cases of hypertriglyceridemia in humans might be caused by defects in GPIHBP1. In a recent study, the exons of GP1HBP1 were sequenced in 160 patients with severe hypertriglyceridemia, and a homozygous G56R mutation was identified in two siblings with chylomicronemia. This mutation was not encountered in 600 normolipidemic Caucasian control subjects or 610 Caucasian patients with hyperlipidemia. Although the finding of a homozygous GPIHBP1 mutation in two siblings was intriguing, recent cell culture studies have suggested that the G56R mutation may not after GPIHBP1 function. Additional sequencing efforts in diverse populations will be required to understand the relevance of GPIHBP1 mutations to human hypertriglyceridemia.