Elevated LDL triglyceride concentrations in subjects heterozygous for the hepatic lipase S267F variant

被引:10
作者
Hegele, RA
Breckenridge, WC
Cox, DW
Maguire, GF
Little, JA
Connelly, PW
机构
[1] Univ Western Ontario, Robarts Res Inst, Blackburn Cardiovasc Genet Lab, London, ON N6A 5K8, Canada
[2] Dalhousie Univ, Dept Biochem, Halifax, NS, Canada
[3] Univ Alberta, Dept Med Genet, Edmonton, AB, Canada
[4] Univ Toronto, St Michaels Hosp, Dept Med, Toronto, ON, Canada
关键词
genetics; lipoproteins; LDL subclasses; lipolysis; lipoprotein lipase;
D O I
10.1161/01.ATV.18.8.1212
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Although naturally occurring loss-of-function mutations in human hepatic lipase (HL) have been described, the biochemical phenotype of heterozygous HL deficiency remains ill defined. This may be due to the relatively small numbers of heterozygous adult carriers of HL mutations in index kindreds. We have identified several new heterozygotes for the catalytically inactive, nonsecreted HL variant S267F in the kindred that was originally ascertained because of hypertriglyceridemia due to the mutant, secreted, circulating apolipoprotein (apo) CII variant apo CII-T. Pairwise comparisons with family controls showed that only the plasma low density lipoprotein triglycerides (LDL TGs) were higher in 11 simple heterozygotes for HL S267F (P=0.002), In contrast, both plasma total TGs and LDL TGs were significantly higher in 12 simple heterozygotes for apo CII-T than in family-matched control subjects (P=0.005 and 0.009, respectively). These findings suggest that the TG content of LDL is increased by heterozygosity fur 2 different: mutations that affect different proteins involved in lipolysis. However, the mechanisms underlying this compositional change in LDL appear to be different for the 2 mutations, because the total TGs are also elevated in subjects heterozygous for apo CII-T but not in subjects heterozygous for HL S267F.
引用
收藏
页码:1212 / 1216
页数:5
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