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Arterioscler Thromb Vasc Biol. 2012 Feb;32(2):459-66. doi: 10.1161/ATVBAHA.111.238493. Epub 2011 Nov 17.

Apolipoprotein B-100-containing lipoprotein metabolism in subjects with lipoprotein lipase gene mutations.

Author information

1
Discovery Medicine CVU CEDD, GlaxoSmithKline, Department of Discovery Medicine, 709 Swedeland Rd, UW2301, King of Prussia, PA 19406, USA. esther.ooi@uwa.edu.au

Abstract

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.

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.

PMID:
22095987
PMCID:
PMC4729373
DOI:
10.1161/ATVBAHA.111.238493
[Indexed for MEDLINE]
Free PMC Article

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