Newly identified missense mutation reduces lipoprotein lipase activity in Taiwanese patients with hypertriglyceridemia

Lipoprotein lipase (LPL)plays a crucial role in the regulation of lipoprote in metabolism by hydrolyzing the core triglycerides of circulating chylomic rons and very low-density lipoprotein. Deficiency in this enzyme usually re sults in disturbances in lipid levels. To understand the molecular defect t hat leads to a functional deficiency of LPL in patients with hypertriglycer idemia, we looked for mutations of the LPL gene by means of single-strand c onformation polymorphism (SSCP) analysis and direct DNA sequencing in 24 pa tients. A single base C-->G substitution in codon 252 of the LPL gene, enco ding a change of a leucine to a valine residue in the mature protein, was f ound in three women who had hypertriglyceridemia and recurrent pancreatitis . Two of these patients, who were homozygous for the L252V mutation, had va riable and occasionally severe hypertriglyceridemia with undetectable or ve ry low LPL activities, respectively. The third woman was heterozygous for t his mutation. All three patients had poor post-heparin LPL activity. Site-d irected mutagenesis experiments Provided in vitro evidence that the mutatio n of codon 252 was was responsible for the loss of LPL activity. In conclus ion, we identified a novel LPL mutation that results in decreased LPL activ ity in Taiwanese patients with hypertriglyceridemia. The assessment of a ca usative link between the mutation and hyperlipidemia awaits further studies .