Lipoprotein Lipase Gene Complex Mutations (1 ¡ú Ile / Glu, Met, ~ ~ (242) ¡ú Of Lys) Led To Lipoprotein Lipase Deficiency

Lipoprotein lipase (LPL) is the key enzyme in the hydrolysis of the triglyceride core of chylomicrons (CM) and very low density lipoproteins (VLDL). LPL is produced by heart, adipose tissue, muscle, as well as in small amounts by many other tissues. Active LPL is a homodimer that is bound to heparan sulfate proteoglycans (HSPG) on the surface of capillary endothelium, with apolipoprotein C- II as a cofactor. Lipoprotein lipase deficiency results in massive accumulation of chylomicrons and profound fasting hypertriglyceridemia (HTG) due to delayed plasma clearance, as well as markedly reduced cholesterol concentrations in low- and high-density lipoproteins. On a normal diet, patients typically exhibit severe chylomicronemia, hepatosplenomegaly, and episodes of abdominal pain and eruptive xanthomas, sometimes complicated by acute pancreatitis, which are usually manifested in childhood. Human LPL gene, located on the short arm of chromosome 8, is composed of 10 exons and 9 introns spanning some 30 kb. Exons one through nine encode 475 amino acids, which contains a signal peptide of 27 amino acids. A predicted molecular model of LPL based on the 3-D structure of pancreatic lipase has been used to identify various functional and structural regions consisting of an N-terminal domain and a distinct C-terminal domain of LPL. The N-terminal domain comprises three-quarters of the sequence, contains several functional domains including â‘ Signal Peptide; â‘¡The catalytic triad of Ser¹³²-His²⁴¹-Asp¹⁵⁶; â‘¢A loop covering the catalytic site of the enzyme that appears to be important for the interaction of LPL with its specific lipid substrate; â‘£apoC- II binding site; ⑤Heparin binding site; â‘¥Four disulfate bridges and two residues of N-linked glycosylation. The distinct C-terminal domain contains the last ～100 animo acids, which mediates the interaction of the enzyme with its lipid substrate. It is important for the dimerization of LPL. LPL activity and mass will decrease when mutations occur in base sequences which encode specific functional domains. Meanwhile, LPL trscription will change when mutations occured in regulatory region or splice site of LPL gene.Familial lipoprotein lipase deficiency is a rare autosomal recessive disorder. The...