Apolipoprotein A-I gene polymorphism associated with premature coronary artery disease and familial hypoalphalipoproteinemia.
Apolipoprotein A-I gene polymorphism associated with premature coronary artery disease and familial hypoalphalipoproteinemia.
复制标题
DOI：
10.1056/nejm198603133141102
复制
发表时间：
1986-03
期刊：
影响因子：
--
通讯作者：
J. Ordovás;E. Schaefer;D. Salem;R. Ward;C. Glueck;C. Vergani;P. Wilson;S. Karathanasis
中科院分区：
文献类型：
--
作者：
J. Ordovás;E. Schaefer;D. Salem;R. Ward;C. Glueck;C. Vergani;P. Wilson;S. Karathanasis
血浆高密度脂蛋白（HDL）胆固醇和载脂蛋白A-I水平降低与早发冠状动脉疾病有关。我们确定了一个PstI限制性内切酶位点侧翼的人载脂蛋白A-I基因在其3'端是多态性的。通过使用载脂蛋白A-I基因探针对Pst I消化的染色体DNA进行基因组印迹分析，确定该位点的存在和缺失分别与3.3-kb和2.2-kb杂交带相关。3.3kb条带出现在123名随机选择的对照组中的4.1%和30名无冠状动脉疾病血管造影证据的受试者中的3.3%。相比之下，在88名60岁之前患有严重冠心病的患者中，血管造影显示，3.3kb条带出现在32%（P <0.0001）。在12例家族性低脂蛋白血症的肾病指标病例中，有8例（P <0.0001）也发现了这种情况。在两个患者组中，产生3.3kb条带的位点的等位基因频率分别为17%和42%，而对照人群中的等位基因频率仅为2%。在家族性低脂蛋白血症患者和冠状动脉疾病患者的一级亲属中，3.3kb条带与HDL胆固醇水平降低相关。在所有冠状动脉疾病患者中，58%的HDL胆固醇水平低于正常值的第10百分位数;然而，当考虑到3.3 kb条带的患者时，这一频率增加到73%。这些发现表明，载脂蛋白A-I和载脂蛋白C-III基因之间区域的多态性可能是早发冠状动脉疾病和家族性低α脂蛋白血症风险的有用标志物。
Decreased plasma high-density-lipoprotein (HDL) cholesterol and apolipoprotein A-I levels have been associated with premature coronary artery disease. We identified a PstI restriction-endonuclease site flanking the human apolipoprotein A-I gene at its 3' end that is polymorphic. The absence and presence of this site, as determined by genomic blotting analysis of PstI-digested chromosomal DNA with the use of an apolipoprotein A-I gene probe, were associated with 3.3-kb and 2.2-kb hybridization bands, respectively. The 3.3-kb band appeared in 4.1 percent of 123 randomly selected control subjects and in 3.3 percent of 30 subjects with no angiographic evidence of coronary artery disease. In contrast, among 88 patients who had severe coronary disease before the age of 60, as documented by angiography, the 3.3-kb band occurred in 32 percent (P less than 0.0001). It was also found in 8 of 12 index cases (P less than 0.0001) of kindreds with familial hypoalphalipoproteinemia. In the two patient groups, the allele frequencies of the site that produced the 3.3-kb band were 17 and 42 percent, respectively, as compared with an allele frequency of only 2 percent in the control populations. Within kindreds with familial hypoalphalipoproteinemia and among first-degree relatives of patients with coronary artery disease, the 3.3-kb band was associated with decreased HDL cholesterol levels. Among all patients with coronary artery disease, 58 percent had HDL cholesterol levels below the 10th percentile of normal values; however, this frequency increased to 73 percent when patients with the 3.3-kb band were considered. These findings indicate that the polymorphism in the region between the apolipoprotein A-I and apolipoprotein C-III genes may be a useful marker for the risk of premature coronary artery disease and familial hypoalphalipoproteinemia.