Hypertriglyceridaemia due to genetic defects in lipoprotein lipase and apolipoprotein C-II


Molecular Disease Branch, National Heart, Lung and Blood Institute, National Institute of Health, 9000 Rockville Pike, Building 10, Room 7N117, Bethesda, MD 20892, USA


Abstract. Hypertriglyceridaemia, as defined by fasting triglyceride levels of > 2.8mmol l-1, is a prevalent dyslipoproteinaemia in our population. The underlying pathophysiological mechanisms that result in elevations of plasma triglycerides are heterogeneous and, in most cases, incompletely understood. However, in a subset of patients presenting with this lipid disorder, the biochemical and genetic defects that lead to hypertriglyceridaemia have been well characterized. These individuals present with the familial chylomicronaemia syndrome, a rare genetic disorder that is inherited as an autosomal recessive trait, and is characterized by severe fasting hypertriglyceridaemia, massive accumulations of chylomicrons in plasma, and recurrent bouts of pancreatitis. The two major causes of the familial chylomicronaemia syndrome are a deficiency of the enzyme, lipoprotein lipase (LPL), or its cofactor, apolipoprotein (apo) C-II. Together, these two proteins initiate the hydrolysis of triglycerides present in chylomicrons and very low density lipoproteins. In the past decade our understanding of the underlying molecular defects that lead to familial chylomicronaemia has been greatly enhanced by the identification of mutations in the genes for LPL and apoC-II. Characterization of these defects has provided new insights into the structure and function of apoC-II and LPL and established the important role that these two proteins play in normal triglyceride metabolism.