Gaw A, Brown E A, Ford I
Department of Pathological Biochemistry, Royal Infirmary, University of Glasgow, UK.
Arterioscler Thromb Vasc Biol. 1998 Dec;18(12):1870-6. doi: 10.1161/01.atv.18.12.1870.
Plasma lipoprotein(a) [Lp(a)] levels are believed to be controlled predominantly by the apolipoprotein(a) [APO(a)] gene, which encodes the apo(a) glycoprotein, a key constituent of the Lp(a) particle. Previously, it has been accepted that the plasma Lp(a) level is inversely proportional to apo(a) length. To examine this relationship in greater detail, 1500 unrelated, homogeneous (sex, race, age, plasma lipids) subjects were studied, from which 769 were identified with a single-expressing APO(a) allele. A bimodal frequency distribution of apo(a) isoforms was observed. As expected, there was a general inverse relationship between apo(a) isoform size and Lp(a) level. However, when groups with equivalent single-expressing apo(a) isoforms were studied, it was clear that although smaller isoforms were associated on average with higher levels, they were also associated with the greatest variability in level. After logarithmic transformation of Lp(a) data, the overall contribution of the apo(a) length polymorphism was calculated to be 38%. However, in subjects with apo(a) isoforms of </=20 kringle-4 (K-4) repeats, only 9% of the variability in Lp(a) concentration is explicable on the basis of the apo(a) length polymorphism. In those with apo(a) isoforms of >20 K-4 repeats, the corresponding contribution is 10%. We conclude that the contribution of the apo(a) isoform size to the control of plasma Lp(a) level is considerably lower than previously calculated, because the variability in plasma Lp(a) concentration is not uniform across the apo(a) size spectrum.
血浆脂蛋白(a)[Lp(a)]水平被认为主要受载脂蛋白(a)[APO(a)]基因控制，该基因编码载脂蛋白(a)糖蛋白，它是Lp(a)颗粒的关键成分。此前，人们一直认为血浆Lp(a)水平与载脂蛋白(a)长度成反比。为了更详细地研究这种关系，我们对1500名无亲属关系、特征均一（性别、种族、年龄、血脂）的受试者进行了研究，其中769人被鉴定为具有单表达APO(a)等位基因。观察到载脂蛋白(a)异构体的双峰频率分布。正如预期的那样，载脂蛋白(a)异构体大小与Lp(a)水平之间存在总体反比关系。然而，当对具有等效单表达载脂蛋白(a)异构体的组进行研究时，很明显，虽然较小的异构体平均与较高水平相关，但它们也与水平的最大变异性相关。对Lp(a)数据进行对数转换后，计算出载脂蛋白(a)长度多态性的总体贡献为38%。然而，在载脂蛋白(a)异构体的kringle-4（K-4）重复次数≤20的受试者中，基于载脂蛋白(a)长度多态性，Lp(a)浓度变异性中只有9%是可以解释的。在载脂蛋白(a)异构体的K-4重复次数>20的受试者中，相应的贡献为10%。我们得出结论，载脂蛋白(a)异构体大小对血浆Lp(a)水平控制的贡献远低于先前计算的结果，因为血浆Lp(a)浓度的变异性在载脂蛋白(a)大小谱中并不均匀。
