ABCA1基因全编码区SNP筛选及外显子7、16 SNP意义的研究

发布时间：2018-02-08 10:59

本文关键词： ATP结合盒转动子A1 胆固醇逆转运高密度脂蛋白动脉粥样硬化冠心病单核苷酸多态性　出处：《第一军医大学》2006年硕士论文　论文类型：学位论文

【摘要】：一．研究背景 ATP结合盒转运子A1(ABCA1)基因，是ABCA亚族成员之一。自Bodzioch M等首次明确ABCA1基因突变是Tangier病的病因以来，目前已经明确ABCA1介导细胞内胆固醇和磷脂外流，在胆固醇逆转运(RCT)和高密度脂蛋白(HDL)生成的起始步骤中起重要作用，是RCT的限速基因，并与动脉粥样硬化(AS)和冠心病(CAD)的发生密切相关。ABCA1基因的单核苷酸多态性(SNP)广泛存在，至今为止，已发现90多个与疾病相关的ABCA1基因突变或SNP位点，这些SNP位点大多分布在基因的编码区，对控制ABCA1基因的表达以及血脂水平的调节和导致AS和CAD的发生起着重要作用。但这些SNP绝大部分的分布特点以及作用机制目前尚不清楚，这正是当前国内外生命科学研究的一个热点。二、研究目的 ABCA1基因有50个外显子，我们实验小组分别对50个外显子SNP位点进行筛选(本人负责第19-34号外显子)，，以发现新的SNP及确定各SNP位点在汉族人中的分布情况。第7号外显子R219K位点在已知的ABCA1基因SNPs中发生率第一，国内对冠脉介入病人未有报告。第16号外显子上相邻位点存在V771M、T774P、K776N 3个SNP位点，较为特殊。因此我们对第7号外显子以及第16号外显子上SNP位点进行重点研究，确定它们的发生率以及各基因型的分布情况，明确它们与血脂水平以及冠心病的发生、冠脉病变的范围和严重程度的关系，以探讨它们影响AS和CAD的可能机制。三．方法
[Abstract]:I. background to the study. The ATP binding cassette transporter A1G ABCA1) gene is a member of the ABCA subfamily. Since Bodzioch M et al first identified the mutation of ABCA1 gene as the etiology of Tangier disease, it has been known that ABCA1 mediates intracellular cholesterol and phospholipid efflux. It plays an important role in the initiation of cholesterol reverse transport (RCT) and high density lipoprotein (HDL) production. It is the rate-limiting gene of RCT, and is closely related to the occurrence of atherosclerosis and coronary heart disease (CAD). The single nucleotide polymorphism of ABCA1 gene is widespread. So far, more than 90 disease-related ABCA1 gene mutations or SNP loci have been found, most of which are located in the coding region of the gene. It plays an important role in controlling the expression of ABCA1 gene, regulating the level of blood lipids and leading to the occurrence of as and CAD. However, the distribution and mechanism of most of these SNP are still unclear. This is a hot spot of life science research at home and abroad. II. Purpose of research. The ABCA1 gene has 50 exons. Our team screened 50 exon SNP loci (I was responsible for exon 19-34 to identify new SNP and determine the distribution of SNP loci in Han Chinese. Exon 7 R219K loci are known. The incidence of ABCA1 gene SNPs was the first. There were 3 SNP loci on the adjacent site of V771MN T774P#en0# K776N on exon 16 in China. Therefore, we focused on the SNP loci in exon 7 and exon 16. In order to explore the possible mechanism of their influence on as and CAD, the incidence rate and the distribution of each genotype were determined, and the relationship between them and the level of blood lipid, the occurrence of coronary heart disease, the extent and severity of coronary artery disease were determined in order to explore the possible mechanism of their influence on as and CAD. III. Methodology
【学位授予单位】：第一军医大学
【学位级别】：硕士
【学位授予年份】：2006
【分类号】：R346

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