APOLIPOPROTEIN A-I GENE POLYMORPHISM AND ATHEROSCLEROSIS

载脂蛋白（apo）A-I是高脂血症的主要蛋白质成分， 密度脂蛋白（HDL）。 高密度脂蛋白已被证明可以促进胆固醇 体外细胞外排。 HDL血浆浓度降低 胆固醇和载脂蛋白A-I与早发冠状动脉 在我们的社会中，由于动脉粥样硬化导致的疾病（CAD）。 遗传HDL 缺乏症（家族性低脂蛋白血症）似乎相当常见 在早发CAD患者中。 载脂蛋白A-I的基因已被分离出来， 表征了 我们的初步研究表明，一种特定的apoA-I 基因多态性，Pst I限制性内切酶消化后检测 使用特定探针，在患有 早发冠心病（32.8%）高于正常对照组（3.9%）， 激酶与遗传性HDL缺乏有关。 这个apoA-I基因 多态性是由于apoA-I，apoC-III基因间的改变， 区域，接近ApoA-I的编码区的3'末端。 我们的具体目标是：1）确定遗传性HDL的患病率 胆固醇和载脂蛋白A-I缺乏症与Pst Ⅰ型载脂蛋白A-I基因多态性 早发CAD患者及其一级亲属使用 标准脂质分析、免疫测定和Southern印迹; 2）评估 早发CAD的风险是否与基因相关 多态性; 3）确定HDL缺乏症， Pst I基因多态性与早发CAD的连锁分析; 4） 通过基因分离和表征异常apoA-I、apoC-III基因复合体 用多种限制性内切酶进行作图研究，并通过克隆和 测序方法 这些研究将使我们能够测试以下内容 假设： 1. Pst Ⅰ apoA-I基因多态性与遗传性HDL相关 缺乏和早发CAD; 2.与Pst I apoA-I基因相关的遗传性HDL缺乏症 多态性是一种常见的家族性脂蛋白紊乱， 过早CAD; 3. Pst I apoA-I基因多态性是由于一个特定的突变， apoA-I、apoC-III基因间区直接或间接（通过 连锁多态性）影响apoA-I合成。

Apolipoprotein (apo) A-I is the major protein constituent of plasma high density lipoproteins (HDL). HDL has been shown to promote cholesterol efflux from cells in vitro. Decreased plasma concentrations of HDL cholesterol and apoA-I have been associated with premature coronary artery disease (CAD) due to atherosclerosis in our society. Genetic HDL deficiency (familial hypoalphalipoproteinemia) appears to be fairly common in patients with premature CAD. The gene for apoA-I has been isolated and characterized. Our preliminary studies indicate that a specific apoA-I gene polymorphism, detected following Pst I restriction enzyme digestion utilizing a specific probe, is significantly more common in subjects with premature CAD (32.8%) than in normal control subjects (3.9%), and in some kindreds is associated with genetic HDL deficiency. This apoA-I gene polymorphism is due to an alteration in the apoA-I, apoC-III intergenic region, near the 3' end of the coding region for ApoA-I. Our specific aims are: 1) to determine the prevalence of genetic HDL cholesterol and apoA-I deficiency and the Pst I apoA-I gene polymorphism in patients with premature CAD and their first degree relatives utilizing standard lipid analysis, immunoassay and Southern blotting; 2) to assess whether the risk of developing premature CAD is associated with the gene polymorphism; 3) to ascertain the relationship between HDL deficiency, the Pst I gene polymorphism, and premature CAD by linkage analysis; 4) to isolate and characterize the abnormal apoA-I, apoC-III gene complex by gene mapping studies with multiple restriction enzymes, and by cloning and sequencing methods. These studies will allow us to test the following hypotheses: 1. The Pst I apoA-I gene polymorphism is associated with genetic HDL deficiency and premature CAD; 2. Genetic HDL deficiency associated with the Pst I apoA-I gene polymorphism is a common familial lipoprotein disorder in patients with premature CAD; 3. The Pst I apoA-I gene polymorphism is due to a specific mutation in the apoA-I, apoC-III intergenic region, which directly or indirectly (via a linked polymorphism) affects apoA-I synthesis.