title: Apolipoprotein B-100-containing lipoprotein metabolism in subjects with lipoprotein lipase gene mutations.
abstract: OBJECTIVE
  We investigated the impact of lipoprotein lipase (LPL) gene mutations on apolipoprotein B (apoB)-100 metabolism.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Discovery Medicine CVU CEDD, GlaxoSmithKline, Department of Discovery Medicine, 709 Swedeland Rd, UW2301, King of Prussia, PA 19406, USA. esther.ooi@uwa.edu.au
authors.forename: Esther M M
authors.initials: EM
authors.lastname: Ooi
authors.forename: Betsy S
authors.initials: BS
authors.lastname: Russell
authors.forename: Eric
authors.initials: E
authors.lastname: Olson
authors.forename: Sam Z
authors.initials: SZ
authors.lastname: Sun
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Diffenderfer
authors.forename: Alice H
authors.initials: AH
authors.lastname: Lichtenstein
authors.forename: Leonard
authors.initials: L
authors.lastname: Keilson
authors.forename: P Hugh R
authors.initials: PH
authors.lastname: Barrett
authors.forename: Ernst J
authors.initials: EJ
authors.lastname: Schaefer
authors.forename: Dennis L
authors.initials: DL
authors.lastname: Sprecher
mesh_terms: D000328:Adult; D000483:Alleles; D053299:Apolipoprotein B-100 / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D015228:Hypertriglyceridemia / Q000209:etiology / Q000378:metabolism; D008071:Lipoprotein Lipase / Q000172:deficiency / Q000235:genetics*; D053419:Lipoproteins, IDL / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D008079:Lipoproteins, VLDL / Q000378:metabolism; D008297:Male; D008659:Metabolic Diseases / Q000150:complications / Q000235:genetics* / Q000378:metabolism*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D014280:Triglycerides / Q000097:blood
chemical_list: D053299:Apolipoprotein B-100; D053419:Lipoproteins, IDL; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D014280:Triglycerides; D008071:Lipoprotein Lipase
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