Lambert M, Assouline L, Feoli-Fonseca J C, Brun N, Delvin E E, Lévy E
Medical Genetics Service, Department of Pediatrics, Sainte-Justine Hospital, University of Montreal, Montreal, Quebec, Canada.
Arterioscler Thromb Vasc Biol. 2001 Jun;21(6):979-84. doi: 10.1161/01.atv.21.6.979.
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.
家族性高胆固醇血症（FH）生化表现的广泛变异性仅部分由低密度脂蛋白受体（LDLR）基因突变的异质性所解释。在本研究中，我们测定了一组携带>15 kb LDLR基因缺失的杂合子儿童（n = 67）的这种生化变异性，并研究了载脂蛋白（apo）E和B等位基因变异对这种表型变异性的影响。与对照组相比，FH患者的总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）和apoB浓度以及TC与高密度脂蛋白胆固醇（HDL-C）比值的方差均增加。然而，在考虑均值后，变异系数显示，FH患者LDL-C和apoB浓度的变异性低于对照组，而两组间TC以及TC与HDL-C比值的变异性相似。ε2/3基因型与FH患者较低的平均TC、LDL-C和apoB浓度相关。这种效应在对照组中的程度小于FH患者。实际上，在FH病例中，TC、LDL-C和apoB总方差中归因于apoE基因座的百分比分别为19.9%、18.1%和11.8%，而在对照组中分别为5.9%、7.4%和6.0%。我们未检测到apoB插入/缺失多态性对FH儿童脂质性状的任何影响。然而，在对照组中，我们观察到apoE和apoB基因型在apoB浓度以及TC与HDL-C比值方面存在强烈的相互作用。我们的研究再次强调了apoE在脂质代谢中的重要作用，并表明等位基因变异对脂质性状的影响取决于背景。
