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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2001;21:979.)
© 2001 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Determinants of Lipid Level Variability in French-Canadian Children With Familial Hypercholesterolemia

Marie Lambert; Linda Assouline; Juan Carlos Feoli-Fonseca; Nathalie Brun; Edgard E. Delvin; Emile Lévy

From the Medical Genetics Service, Department of Pediatrics (M.L., L.A., J.C.F.-F., N.B.), the Department of Clinical Biochemistry (E.E.D.), and the Department of Nutrition (E.L.), Sainte-Justine Hospital, University of Montreal, Montreal, Quebec, Canada.

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 2/3 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.

Key Words: familial hypercholesterolemia • children • apoE • apoB • allelic variations