HDAC9对血管内皮细胞基因表达谱的影响及其基因多态性与大动脉粥样硬化的相关性

项目名称： HDAC9对血管内皮细胞基因表达谱的影响及其基因多态性与大动脉粥样硬化的相关性

项目编号： No.81460184

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 廖小平

作者单位： 海南医学院

项目金额： 48万元

中文摘要： 全基因关联分析和动脉粥样硬化斑块的分析结果表明组蛋白脱乙酰基酶9(HDAC9)与大动脉粥样硬化型脑梗死(LAA-S)关联，并具有促进大动脉粥样硬化的可能性。但我国尚缺乏各地区HDAC9基因多态性与LAA-S的病例相关性研究，且HDAC9与LAA-S的相关性的分子机制目前尚未阐明。本项目拟通过海南地区LAA-S患者、健康人群和长寿老人的对照研究，分析HDAC9基因单核苷酸多态性(SNPs)及单倍型与LAA-S的关联性，阐明其基因多态性及单倍型与LAA-S的关系；同时拟建立HDAC9表达上调或下调的血管内皮细胞模型，并用RNA测序技术分析HDAC9对血管内皮细胞基因表达谱的影响，筛查HDAC9调控的靶基因及相关的代谢通路，研究血管内皮细胞基因谱变化特点与其增殖和凋亡的关系。本项目有望利用海南原住民人群的独特性检验HDAC9与动脉粥样硬化的相关性并进一步阐明HDAC9在LAS-S的发生分子机制。

中文关键词： 动脉粥样硬化性脑梗死；大动脉粥样硬化；组蛋白脱乙酰基酶9；基因多态性；血管内皮细胞

英文摘要： Genome-wide association study and atherosclerotic plaques pathological analysis showed histone deacetylase 9 (HDAC9) associated with large artery atherosclerosis stroke (LAA-S). HDAC9 may promote atherosclerosis of large artery, but its molecular mechanism has not been fully elucidated. On the other hand, the data of HDAC9 gene polymorphism with LAA-S is still lack in the different region in China. Therefore, we will also analyze the single nucleotide polymorphism (SNPs) and haplotypes of HDAC9 gene in LAA-S patients, control population and longevity population in hainan province to study the association of SNPs and haplotype in HDAC9 with LAA-S. Furthermore, this study will analyze the features of gene expression profiles of the vascular endothelial cells in the situation of up- or down-regulation of HDAC9 by using RNA sequencing technology to screen the target genes and metabolic pathways associated with HDAC9 regulation, and will also explore the relationship between the changes of gene profiling and growth and apoptosis of vascular endothelial cell. This study will provide new scientific evidence for the association of HDAC9 SNPs with LAA-S in Hainan population and further elucidating the molecular mechanisms of HDAC9 in the occurrence of atherosclerosis.

英文关键词： atherosclerosis stroke;large artery atherosclerosis;HDAC9;gene polymorphism;vascular endothelial cell