THE APOLIPOPROTEIN(A) KRINGLE-IV REPEATS WHICH DIFFER FROM THE MAJOR REPEAT KRINGLE ARE PRESENT IN VARIABLY-SIZED ISOFORMS
THE APOLIPOPROTEIN(A) KRINGLE-IV REPEATS WHICH DIFFER FROM THE MAJOR REPEAT KRINGLE ARE PRESENT IN VARIABLY-SIZED ISOFORMS
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DOI：
10.1093/hmg/2.4.361
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发表时间：
1993-04-01
影响因子：
3.5
通讯作者：
KOSCHINSKY, ML
中科院分区：
文献类型：
--
作者：
VANDERHOEK, YY;WITTEKOEK, ME;KOSCHINSKY, ML
血浆脂蛋白（a）[Lp（a）]水平升高与人群中动脉粥样硬化的发生相关。载脂蛋白（a）[apo（a）; Lp（a）的区别性蛋白组分]的特征在于与纤溶酶原的kringle IV非常相似的序列的多个重复。在人群中观察到的不同大小的Lp（a）亚型已被证明是由于apo（a）中重复kringle IV单位数量的差异而发生的。使用人肝mRNA的PCR分析，我们分析了来自10个无关个体的载脂蛋白（a），以确定是否存在Kringle IV重复序列#1和#30-#37。根据已发表的一个个体的载脂蛋白（a）cDNA序列，这些Kringle在氨基酸序列上都与主要Kringle IV重复序列有一定程度的不同，主要Kringle IV重复序列存在于许多相同的重复拷贝中。我们发现对应于apo（a）kringle IV重复序列#1和#30-#37的序列存在于所有研究的个体中。这表明，Lp（a）亚型大小和血浆Lp（a）水平之间观察到的反比关系是由不同数量的相同kringle IV重复序列介导的，其机制尚未确定。在这项研究的过程中，我们确定了载脂蛋白（a）kringle IV重复序列#37中的Met->Thr多态性。Met和Thr等位基因频率分别为0.58和0.42。我们没有观察到Met -> Thr取代与血浆Lp（a）水平或apo（a）转录物大小之间的相关性。
Elevated levels of plasma lipoprotein(a) [Lp(a)] have been correlated with the development of atherosclerosis in human populations. Apolipoprotein(a) [apo(a); the distinguishing protein component of Lp(a)] is characterized by multiple repeats of a sequence that closely resembles kringle IV of plasminogen. Variably-sized Lp(a) isoforms that are observed in the human population have been shown to occur as a result of differences in the numbers of the repeated kringle IV units in apo(a). Using PCR analysis of human liver mRNA, we have analyzed apo(a) from 10 unrelated individuals in order to determine the presence or absence of kringle IV repeat #1, and #30-#37. Based on the apo(a) cDNA sequence published for one individual, these kringles all differ to some degree in amino acid sequence from the major kringle IV repeat, which is present in a number of identically repeated copies. We found that sequences corresponding to apo(a) kringle IV repeat #1, and #30-#37 were present in all individuals studied. This suggests that the inverse relationship that has been observed between Lp(a) isoform size and plasma Lp(a) levels is mediated by different numbers of identical kringle IV repeats, by an as yet undetermined mechanism. During the course of this study, we identified a Met-->Thr polymorphism in the apo(a) kringle IV repeat #37. The calculated frequencies of the Met and Thr alleles were 0.58 and 0.42 respectively. We did not observe a correlation between the Met --> Thr substitution and either plasma Lp(a) levels, or apo(a) transcript size.