Apolipoprotein B-100–Containing Lipoprotein Metabolism in Subjects With Lipoprotein Lipase Gene Mutations

• Published in: Arteriosclerosis, thrombosis, and vascular biology Vol. 32; no. 2; pp. 459 - 466
• Main Authors: Ooi, Esther M.M., Russell, Betsy S., Olson, Eric, Sun, Sam Z., Diffenderfer, Margaret R., Lichtenstein, Alice H., Keilson, Leonard, Barrett, P. Hugh R., Schaefer, Ernst J., Sprecher, Dennis L.
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Heart Association, Inc 01.02.2012; Lippincott Williams & Wilkins
• Subjects: Adult; Alleles; Apolipoprotein B-100 - metabolism; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Case-Control Studies; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Female; Fundamental and applied biological sciences. Psychology; General aspects; Genotype; Heterozygote; Homozygote; Humans; Hypertriglyceridemia - etiology; Hypertriglyceridemia - metabolism; Lipoprotein Lipase - deficiency; Lipoprotein Lipase - genetics; Lipoproteins, IDL - metabolism; Lipoproteins, LDL - metabolism; Lipoproteins, VLDL - metabolism; Male; Medical sciences; Metabolic Diseases - complications; Metabolic Diseases - genetics; Metabolic Diseases - metabolism; Middle Aged; Mutation - genetics; Triglycerides - blood; Vertebrates: cardiovascular system; Human; apolipoproteins; Enzyme; Triacylglycerol lipase; Metabolic diseases; Lipids; Cardiovascular disease; Esterases; Hyperlipoproteinemia; Lipoprotein lipase; Lipoprotein; Metabolism; Carboxylic ester hydrolases; Vascular disease; Apolipoprotein B; lipases; Atherosclerosis; Hydrolases; gene mutations; Mutation; Dyslipemia
• ISSN: 1079-5642; 1524-4636; 1524-4636
• DOI: 10.1161/ATVBAHA.111.238493

OBJECTIVE—We investigated the impact of lipoprotein lipase (LPL) gene mutations on apolipoprotein B (apoB)-100 metabolism. METHODS AND RESULTS—We studied 3 subjects with familial LPL deficiency; 14 subjects heterozygous for the LPL gene mutations Gly188Glu, Trp64Stop, and Ile194Thr; and 10 control subjects. Very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and low-density lipoprotein (LDL)-apoB-100 kinetics were determined in the fed state using stable isotope methods and compartmental modeling. Compared with controls, familial LPL deficiency had markedly elevated plasma triglycerides and lower VLDL-apoB-100 fractional catabolic rate (FCR), IDL-apoB-100 FCR, VLDL-to-IDL conversion, and VLDL-apoB-100 production rate (P<0.01). Compared with controls, Gly188Glu had higher plasma triglyceride and VLDL- and IDL-apoB-100 concentrations and lower VLDL- and IDL-apoB-100 FCR (P<0.05). Plasma triglycerides were not different, but IDL-apoB-100 concentration and production rate and VLDL-to-IDL conversion were lower in Trp64Stop compared with controls (P<0.05). No differences between controls and Ile194Thr were observed. CONCLUSION—Our results confirm that hypertriglyceridemia is a key feature of familial LPL deficiency. This is due to impaired VLDL- and IDL-apoB-100 catabolism and VLDL-to-IDL conversion. Single-allele mutations of the LPL gene result in modest to elevated plasma triglycerides. The changes in plasma triglycerides and apoB-100 kinetics are attributable to the effects of the LPL genotype.