Miserez A R, Laager R, Chiodetti N, Keller U
Department of Research, University Hospital, Basel, Switzerland.
J Lipid Res. 1994 Apr;35(4):574-83.
Familial defective apolipoprotein B-100 (FDB) is caused by a single G-to-A substitution at nucleotide 10,708 leading to an arginine to glutamine change at amino acid 3,500 of the apolipoprotein B-100 and thus, a reduced binding of the apolipoprotein B to the low density lipoprotein (LDL) receptor. In the present study, the prevalence of FDB in Switzerland was estimated, on the one hand, from a sample of 728 healthy volunteers whose origin was spread out over the entire German, French, and Romansh speaking parts of the country, and, on the other hand, from 142 unrelated Swiss families with primary hypercholesterolemia comprising 520 individuals. Using polymerase chain reaction (PCR)-based methods, three individuals were identified with the point mutation in the sample of volunteers, equivalent to a prevalence of approximately 1/240 (90% confidence interval: 1.51 x 10(-3)-1.03 x 10(-2)). The frequency of FDB in the sample of hypercholesterolemic subjects was 7/142, yielding a prevalence of approximately 1/190 extrapolated to the general population (90% confidence interval: 2.63 x 10(-3)-9.17 x 10(-2)). The combined prevalence based on both samples was 1/209. Thus, the investigated point mutation was highly prevalent in Switzerland and appeared to be more frequent than in other populations studied hitherto. Furthermore, the presence of the mutation was not necessarily associated with an elevation of serum cholesterol levels, particularly in young individuals. While in the non-affected volunteers cholesterol levels increased between the age of 19 and 23 years by 0.22 mmol/l or by 5.6% (P = 0.001), this phenomenon was even more pronounced in individuals with FDB. The three volunteers with the point mutation demonstrated an increase in total cholesterol concentrations by 1.30 mmol/l or by 25% within 2 years, suggesting that, in the early twenties, cholesterol concentrations increase markedly from normal to elevated levels. Considering the estimated high prevalence and the relative ease of PCR-based tests, screening for FDB may become a standard procedure in patients with suggested familial forms of hypercholesterolemia.
家族性载脂蛋白B - 100缺陷（FDB）是由核苷酸10708处的单个G到A替换引起的，导致载脂蛋白B - 100的第3500位氨基酸处的精氨酸变为谷氨酰胺，从而使载脂蛋白B与低密度脂蛋白（LDL）受体的结合减少。在本研究中，一方面，从728名健康志愿者的样本中估计了FDB在瑞士的患病率，这些志愿者的来源分布在该国讲德语、法语和罗曼什语的整个地区；另一方面，从142个原发性高胆固醇血症的瑞士无关家庭（共520人）中进行估计。使用基于聚合酶链反应（PCR）的方法，在志愿者样本中鉴定出3名携带该点突变的个体，患病率约为1/240（90%置信区间：1.51×10⁻³ - 1.03×10⁻²）。高胆固醇血症患者样本中FDB的频率为7/142，推断在一般人群中的患病率约为1/190（90%置信区间：2.63×10⁻³ - 9.17×10⁻²）。基于两个样本的合并患病率为1/209。因此，所研究的点突变在瑞士非常普遍，而且似乎比迄今为止研究的其他人群更为常见。此外，该突变的存在不一定与血清胆固醇水平升高相关，尤其是在年轻人中。在未受影响的志愿者中，胆固醇水平在19岁至23岁之间升高了0.22 mmol/L，即升高了5.6%（P = 0.001），而在患有FDB的个体中这种现象更为明显。3名携带点突变的志愿者在2年内总胆固醇浓度升高了1.30 mmol/L，即升高了25%，这表明在二十出头时胆固醇浓度会从正常水平显著升高到升高水平。考虑到估计的高患病率以及基于PCR检测相对容易，对疑似家族性高胆固醇血症患者进行FDB筛查可能会成为标准程序。
