Workshop II-7 - Lipoprotein Metabolism: Integration of Lipoprotein Metabolism Abstract: 139 Citation: Atherosclerosis Supplement 2009, Vol. 10, Issue 2
LIPOPROTEIN KINETICS IN SUBJECTS WITH LIPOPROTEIN LIPASE (LPL) GENE MUTATIONS E Ooi1, D Sprecher2, E Schaefer3, M Diffenderfer3, N Matthan3, H Barrett1 1
University of Western Australia, Perth; 2GlaxoSmithKline, King of Prussia; 3Tufts University, Boston, MA Aim To examine VLDL, IDL and LDL apoB kinetics in subjects with LPL gene mutations. Methods 14 subjects heterozygous for LPL gene mutations (5 had a mutation at amino acid residue (AAR) 64 in exon 3 , 5 had a mutation at AAR 194 in exon 5  and 4 had a mutation at AAR 188 in exon 5 ) and 10 age/sex matched healthy controls (HC) were studied. VLDL, IDL and LDL apoB kinetics were examined in the fed state. Results Compared with HC, 188 had higher fasting and postprandial plasma triglycerides (TG). VLDL cholesterol was higher and HDL cholesterol, lower. 188 also had elevated VLDL and IDL apoB levels. This was due to lower VLDLapoB production (PR; -35% p<0.01), and VLDL and IDL apoB fractional catabolic rates (-70% and -62%, respectively p<0.01). Similar lipoprotein and kinetic differences were observed when 188 was compared with 64 and 194 (p<0.05). Compared with HC, 64 had lower IDLapoB level as a consequence of reduced VLDL to IDL conversion (p<0.01). Similar lipoprotein and kinetic differences were observed when 64 was compared with 188 and 194 (p<0.05). There were no differences between HC and 194. LDL apoB level and kinetics were not different between groups. Conclusions Mutation 188 was associated with elevated fasting and postprandial TG. This was related to reduced VLDL and IDL particle catabolism. Mutation 64 was not associated with elevated TG or impaired VLDL catabolism. This mutation, however, altered VLDL to IDL particle conversion. Future studies with appropriate interventions, particularly in subjects with hypertriglyceridemia, are warranted. Funding: This study was funded by a research grant from the National Institutes of Health.