Perombelon Y F, Soutar A K, Knight B L
MRC Lipoprotein Team, Hammersmith Hospital, London, United Kingdom.
J Clin Invest. 1994 Apr;93(4):1481-92. doi: 10.1172/JCI117126.
Plasma lipoprotein(a) (Lp(a)) concentrations vary considerably between individuals. To examine the variation for products of the same and different apolipoprotein(a) (apo(a)) alleles, conditions were established whereby phenotyping immunoblots could be used to estimate the concentration of Lp(a) associated with the constituent apo(a) isoforms. In these studies 28 distinct isoforms were identified, each differing by a single kringle IV unit. Tracking the isoforms through 10 families showed that there could be up to 200-fold difference in the Lp(a) concentration associated with the same-sized isoform produced from different alleles. In contrast there was typically < 2.5-fold variation in the Lp(a) concentration associated with the same allele. However, there were four occasions where the concentration associated with a particular allele was reduced below the typical range from one generation to the next. A nonlinear, inverse trend with isoform size was apparently superimposed upon the other factors that determine Lp(a) concentration. Inheritance of familial hypercholesterolemia or familial-defective apoB100 had little consistent effect upon Lp(a) concentration. In both the families and in other unrelated individuals the distribution of isoforms and their associated concentrations provided evidence for the presence of at least two and possibly more subpopulations of apo(a) alleles with different sizes and expression.
血浆脂蛋白(a) [Lp(a)]浓度在个体间差异很大。为了研究相同和不同载脂蛋白(a) [apo(a)]等位基因产物的差异,建立了相关条件,以便通过表型免疫印迹法估算与组成型apo(a)异构体相关的Lp(a)浓度。在这些研究中,鉴定出了28种不同的异构体,每种异构体相差一个单个的kringle IV单位。对10个家族的异构体进行追踪研究发现,由不同等位基因产生的相同大小异构体所关联的Lp(a)浓度可能相差高达200倍。相比之下,与相同等位基因相关的Lp(a)浓度通常变化小于2.5倍。然而,有4次特定等位基因所关联的浓度在代际间降至典型范围以下。除了其他决定Lp(a)浓度的因素外,异构体大小与Lp(a)浓度之间显然还呈现出非线性的反向趋势。家族性高胆固醇血症或家族性缺陷型载脂蛋白B100的遗传对Lp(a)浓度几乎没有一致的影响。在家族成员和其他无关个体中,异构体及其相关浓度的分布都证明了存在至少两个、可能更多具有不同大小和表达的apo(a)等位基因亚群。