Pimstone S N, Defesche J C, Clee S M, Bakker H D, Hayden M R, Kastelein J J
Department of Medical Genetics, University of British Columbia, Vancouver, Canada.
Arterioscler Thromb Vasc Biol. 1997 May;17(5):826-33. doi: 10.1161/01.atv.17.5.826.
Familial defective apolipoprotein B-100 (FDB) is a dominantly inherited genetic disorder resulting from a point mutation in the apolipoprotein (apo) B gene and is associated with significantly elevated plasma total and LDL cholesterol levels. Despite numerous descriptions outlining the phenotype of children with familial hypercholesterolemia (FH), no study has described the biochemical and clinical phenotype in a cohort of children with FDB. The phenotypes of FH and FDB, therefore, have not been compared in children. We have studied a cohort of 38 Dutch children (all <20 years old) with FDB from 21 different families. Lipid and lipoprotein levels and the clinical phenotype were compared with 97 age-matched FH heterozygotes, as defined by molecular analysis, and with age-matched non-FDB, non-FH control subjects. Female FDB carriers (n=23) had significantly lower total cholesterol (P<.001), LDL cholesterol (P=.001), total cholesterol:HDL ratio (P<.001), and apoB levels (P=.001) than age-matched female FH heterozygotes (n=50). Similar results were noted in male FDB carriers (n=15) compared with male FH heterozygotes (n=47; P=.005, P=.007, P=.014, and P=.074, respectively). Within the FDB group, female FDB heterozygotes had higher LDL cholesterol (P=.038) and a trend to higher total cholesterol levels (P=.165) than age-matched males. Both male and female FDB carriers had significantly higher total cholesterol, LDL cholesterol, and total cholesterol:HDL ratio than age- and sex-matched control subjects, which was evident even in children <10 years of age, providing additional evidence that this mutation is penetrant in early life. These results provide evidence for a milder biochemical phenotype in children with FDB than in children with FH. The phenotype observed is intermediate between that of control subjects and FH heterozygotes matched for age and sex. As the incidence of coronary artery disease is related to both the extent and duration of cholesterol elevation, our findings might explain in part the lower incidence of clinical atherosclerosis seen in adults with this condition than in adults with FH.
家族性载脂蛋白B-100缺陷（FDB）是一种常染色体显性遗传疾病，由载脂蛋白（apo）B基因的点突变引起，与血浆总胆固醇和低密度脂蛋白胆固醇水平显著升高相关。尽管已有大量描述家族性高胆固醇血症（FH）患儿表型的研究，但尚无研究描述FDB患儿队列的生化和临床表型。因此，尚未对儿童FH和FDB的表型进行比较。我们研究了来自21个不同家庭的38名荷兰FDB患儿（均<20岁）。将脂质和脂蛋白水平以及临床表型与97名经分子分析定义的年龄匹配的FH杂合子，以及年龄匹配的非FDB、非FH对照受试者进行比较。女性FDB携带者（n = 23）的总胆固醇（P <.001）、低密度脂蛋白胆固醇（P =.001）、总胆固醇：高密度脂蛋白比值（P <.001）和载脂蛋白B水平（P =.001）显著低于年龄匹配的女性FH杂合子（n = 50）。与男性FH杂合子（n = 47；P分别为.005、.007、.014和.074）相比，男性FDB携带者（n = 15）也有类似结果。在FDB组中，与年龄匹配的男性相比，女性FDB杂合子的低密度脂蛋白胆固醇更高（P =.038），总胆固醇水平有升高趋势（P =.165）。男性和女性FDB携带者的总胆固醇、低密度脂蛋白胆固醇和总胆固醇：高密度脂蛋白比值均显著高于年龄和性别匹配的对照受试者，这在10岁以下儿童中也很明显，进一步证明这种突变在生命早期具有外显率。这些结果为FDB患儿的生化表型比FH患儿更轻提供了证据。观察到的表型介于年龄和性别匹配的对照受试者与FH杂合子之间。由于冠状动脉疾病的发病率与胆固醇升高的程度和持续时间相关，我们的研究结果可能部分解释了患有这种疾病的成年人临床动脉粥样硬化发病率低于FH成年人的原因。
