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Determinants of lipid level variability in French-Canadian children with familial hypercholesterolemia.
- Source :
-
Arteriosclerosis, thrombosis, and vascular biology [Arterioscler Thromb Vasc Biol] 2001 Jun; Vol. 21 (6), pp. 979-84. - Publication Year :
- 2001
-
Abstract
- The wide variability in the biochemical expression of familial hypercholesterolemia (FH) is only partly explained by mutational heterogeneity in the low density lipoprotein receptor (LDLR) gene. In the current study, we measured this biochemical variability in a group of children heterozygous for the >15-kb LDLR gene deletion (n=67) and examined the contribution of apolipoprotein (apo) E and B allelic variations to this phenotypic variability. Variances of total cholesterol (TC), LDL-C, and apoB concentrations and of the ratio of TC to high density lipoprotein cholesterol (HDL-C) were increased in FH subjects compared with controls. However, after taking the means into account, the coefficients of variation showed that the variability of LDL-C and apoB concentrations was smaller for FH than for controls and that the variability of TC and of the ratio TC to HDL-C was similar between both groups. The epsilon2/3 genotype was associated with lower mean TC, LDL-C, and apoB concentrations in FH. The magnitude of this effect was smaller in controls than in FH. Indeed, the percentages of total variance of TC, LDL-C, and apoB attributable to the apoE locus were 19.9%, 18.1%, and 11.8%, respectively, in FH cases and 5.9%, 7.4%, and 6.0%, respectively, in controls. We did not detect any effect of the apoB insertion/deletion polymorphism on lipid traits in FH children. However, in controls, we observed a strong interaction between apoE and apoB genotypes on apoB concentrations and on TC to HDL-C ratios. Our study reemphasizes the important role of apoE in lipid metabolism and illustrates that the effects of allelic variations on lipid traits are context dependent.
- Subjects :
- Apolipoproteins B blood
Apolipoproteins B genetics
Apolipoproteins E blood
Canada
Child
Cholesterol blood
Cholesterol, HDL blood
Cholesterol, LDL blood
Female
France ethnology
Genetic Variation
Genotype
Humans
Male
Mutagenesis, Insertional
Sequence Deletion
Apolipoproteins E genetics
Hyperlipoproteinemia Type II blood
Hyperlipoproteinemia Type II genetics
Lipids blood
Subjects
Details
- Language :
- English
- ISSN :
- 1524-4636
- Volume :
- 21
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Arteriosclerosis, thrombosis, and vascular biology
- Publication Type :
- Academic Journal
- Accession number :
- 11397707
- Full Text :
- https://doi.org/10.1161/01.atv.21.6.979