Kamboh M I, Ferrell R E, Kottke B A
Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, PA 15621.
Am J Hum Genet. 1991 Nov;49(5):1063-74.
Elevated plasma lipoprotein (a) (LP(a] levels are an independent predictor of the development of premature atherosclerosis in humans. The LP(a) particle consists of two disulfide-linked proteins, apolipoprotein (APO) B and APO(a). The APO(a) is a highly glycosylated protein which carries the LP(a) antigen. Genetic polymorphism in the APO(a) molecule has been reported, and, depending on the sensitivity of the method used, 6-11 alleles at the APO(a) structural locus have been documented in the literature. In this investigation, we have used a high-resolution SDS-agarose electrophoresis method followed by immunoblotting to screen APO(a) polymorphism in 54 families with 130 offspring. This method identified a total of 23 different APO(a) isoforms, and their genetic basis was confirmed in families. In addition to the detectable products of 23 APO(a) alleles, the family data predict the existence of a "null" allele. Of the total 270 individuals tested, 209 (77.4%) revealed double-banded phenotypes and 61 (22.6%) revealed single-banded phenotypes. In the unrelated sample of 140 individuals, however, 114 (81.4%) and 26 (18.6%) had double- and single-banded phenotypes, respectively. When the segregation pattern of single-banded phenotypes in the unrelated sample was followed in families, only nine (6.4%) were found to be true homozygotes, and the remaining 17 (12.2%) were classified as heterozygotes for the null allele. Of the 276 possible phenotypes predicted for 23 alleles in a large population, we observed 115 (42%) phenotypes in our restricted sample. On the basis of our results from the family data, we hypothesize the existence of at least 24 alleles, including a null allele, at the APO(a) structural locus.(ABSTRACT TRUNCATED AT 250 WORDS)
血浆脂蛋白(a)[LP(a)]水平升高是人类过早发生动脉粥样硬化的独立预测指标。LP(a)颗粒由两种通过二硫键连接的蛋白质组成，即载脂蛋白(APO)B和APO(a)。APO(a)是一种高度糖基化的蛋白质，携带LP(a)抗原。文献报道了APO(a)分子中的基因多态性，根据所用方法的灵敏度，文献中记录了APO(a)结构位点的6 - 11个等位基因。在本研究中，我们采用高分辨率SDS - 琼脂糖电泳方法，随后进行免疫印迹，对54个家庭的130名后代进行APO(a)多态性筛查。该方法共鉴定出23种不同的APO(a)异构体，并在家庭中证实了它们的遗传基础。除了23个APO(a)等位基因的可检测产物外，家庭数据预测存在一个“无效”等位基因。在总共检测的270名个体中，209名(77.4%)表现为双条带表型，61名(22.6%)表现为单条带表型。然而，在140名无关个体的样本中，分别有114名(81.4%)和26名(18.6%)表现为双条带和单条带表型。当在家庭中追踪无关样本中单条带表型的分离模式时，仅发现9名(6.4%)为真正的纯合子，其余17名(12.2%)被归类为无效等位基因的杂合子。在大量人群中23个等位基因预测的276种可能表型中，我们在受限样本中观察到115种(42%)表型。根据我们家庭数据的结果，我们推测在APO(a)结构位点至少存在24个等位基因，包括一个无效等位基因。(摘要截断于250字)
