Martín S, Ladona M G, Pedro-Botet J, Covas M I, Rubiés-Prat J
Unitat de Lipids i Epidemiologia Cardiovascular, IMIM, Universidad Autónoma de Barcelona, Spain.
Clin Chim Acta. 1998 Oct;277(2):191-205. doi: 10.1016/s0009-8981(98)00126-0.
A sodium dodecyl sulphate-agarose apolipoprotein(a) [apo(a)] phenotyping method was set up to attain accurate scanning densitometry of proteins. Serum samples from 99 healthy Spanish men were analysed and twenty-five different apo(a) isoforms (12 to 37 kringle 4 repeats) were detected. Double-band phenotypes accounted for 39.4% (n = 39) and three different patterns of protein expression were identified: pattern A (20.5% of double-band phenotyped samples) predominantly expressed the highest molecular weight isoform; pattern B (53.9%) mainly the lowest molecular weight isoform, and pattern AB (25.6%), expressed both isoforms equally. A significant linear association between expression pattern and lipoprotein(a) [Lp(a)] concentration > or = 0.30 g/l was observed. Single-band phenotyped samples (n = 60) were stratified according to apo(a) kringle 4 repeat categories and showed that 90% of isoforms < 20 K4 repeats had high Lp(a) concentrations (> or = 0.30 g/l), whereas isoforms with 20 to 24 or more than 24 kringle 4 repeats had Lp(a) concentrations > or = 0.30 g/l in 47% and 14%, respectively. A logistic regression model was fitted to test the association between apo(a) size, expression pattern and Lp(a) concentration. In this model, apo(a) isoform < 25 kringle 4 repeats was significantly associated with serum Lp(a) concentration > or = 0.30 g/l in both single and double-band phenotyped samples (odds ratio = 8.9, p < 0.001). In the latter, a differential expression pattern with respect to smaller size isoforms (pattern AB vs A) was significantly associated with Lp(a) concentration > or = 0.30 g/l (odds ratio = 17.97, P = 0.045). Heterogeneity in protein apo(a) size expressed according to kringle 4 repeat number could be categorized in heterozygous phenotypes as three patterns. When small-sized isoform was expressed (pattern B) or both isoforms were equally expressed (pattern AB), the probability of having Lp(a) > or = 0.30 g/l is higher.
建立了一种十二烷基硫酸钠-琼脂糖载脂蛋白(a)[apo(a)]表型分析方法，以实现蛋白质的准确扫描密度测定。对99名健康西班牙男性的血清样本进行分析，检测到25种不同的apo(a)异构体(12至37个kringle 4重复序列)。双带表型占39.4%(n = 39)，并鉴定出三种不同的蛋白质表达模式：模式A(双带表型样本的20.5%)主要表达分子量最高的异构体；模式B(53.9%)主要是分子量最低的异构体，模式AB(25.6%)则等量表达两种异构体。观察到表达模式与脂蛋白(a)[Lp(a)]浓度≥0.30 g/l之间存在显著的线性关联。单带表型样本(n = 60)根据apo(a) kringle 4重复类别进行分层，结果显示，90%的<20个K4重复的异构体具有高Lp(a)浓度(≥0.30 g/l)，而具有20至24个或超过24个kringle 4重复的异构体，Lp(a)浓度≥0.30 g/l的比例分别为47%和14%。拟合逻辑回归模型以检验apo(a)大小、表达模式与Lp(a)浓度之间的关联。在该模型中，<25个kringle 4重复的apo(a)异构体在单带和双带表型样本中均与血清Lp(a)浓度≥0.30 g/l显著相关(比值比 = 8.9，p < 0.001)。在双带表型样本中，相对于较小尺寸异构体的差异表达模式(模式AB与模式A)与Lp(a)浓度≥0.30 g/l显著相关(比值比 = 17.97，P = 0.045)。根据kringle 4重复数表达的apo(a)蛋白质大小的异质性在杂合表型中可分为三种模式。当表达小尺寸异构体(模式B)或等量表达两种异构体(模式AB)时，Lp(a)≥0.30 g/l的概率更高。
