Hong S H, Min W K, Cheon S I, Lee C C, Song J, Kim J Q
Department of Molecular Biology, Seoul National University, Korea.
Mol Cells. 1998 Oct 31;8(5):544-9.
In view of the clinical importance of lipoprotein(a) [(Lp(a)] in coronary artery disease (CAD), we investigated the apo(a) size polymorphism, sequence polymorphisms of five base repeats [(TTTTA)n] in the noncoding region, and of Met/Thr in the coding region of the apolipoprotein(a) [apo(a)] gene. The apo(a) polymorphisms were examined in 184 Korean patients with CAD and 121 healthy subjects. In size polymorphism, there was an inverse association between plasma Lp(a) levels and the apo(a) isoforms in the CAD group (p < 0.005). For (TTTTA)n sequence polymorphism, subjects with the 8/8 genotype were most frequently observed in the two groups. Plasma Lp(a) levels showed a significant difference between the 8/5 versus the 8/8 genotype in the CAD group. On the other hand, Lp(a) levels varied significantly among the genotypes of a Met/Thr polymorphism in normal controls (P < 0.01). The heterozygous genotype had an intermediate level of Lp(a) between the two homozygous genotypes, thereby showing gene dosage effect. Thus, it is possible that the apo(a) polymorphisms are responsible for variations in the Lp(a) levels.
鉴于脂蛋白(a)[Lp(a)]在冠状动脉疾病(CAD)中的临床重要性,我们研究了载脂蛋白(a)[apo(a)]基因的apo(a)大小多态性、非编码区五个碱基重复序列[(TTTTA)n]的序列多态性以及编码区Met/Thr的序列多态性。在184例韩国CAD患者和121名健康受试者中检测了apo(a)多态性。在大小多态性方面,CAD组血浆Lp(a)水平与apo(a)异构体之间存在负相关(p < 0.005)。对于(TTTTA)n序列多态性,两组中最常观察到的是8/8基因型的受试者。CAD组中,8/5基因型与8/8基因型之间的血浆Lp(a)水平存在显著差异。另一方面,正常对照组中,Met/Thr多态性各基因型之间的Lp(a)水平差异显著(P < 0.01)。杂合基因型的Lp(a)水平介于两种纯合基因型之间,表现出基因剂量效应。因此,apo(a)多态性可能是导致Lp(a)水平变化的原因。