ABO基因多态性与大动脉粥样硬化性脑梗死的相关性及分子机制研究

Stroke is the first leading cause of adult disability and the second cause of death worldwide. Approximately 70%-80% of all strokes are ischemic.The large artery atherosclerotic stroke is the leading subtype of ischemic stroke. Recently, a large-scale genome-wide association study(GWAS) found that a single nucleotide polymorphisms(rs505922) on ABO gene was significantly associated with the large artery atherosclerotic stroke in European populations. However, the molecular mechanisms of this association is still unclear, and epidemiological investigation found that ABO gene had siginificant regional and ethnic differences. Thus, we aim to carry out a case-control study based on our former work and fine-map the ABO gene to assess the associations between ABO gene polymorphism and the large artery atherosclerotic stroke risk and prognosis. In addition, we will evaluate the gene – gene and gene-environment interactions and will establish a multifactor prediction model of the large artery atherosclerotic stroke. Moreover we will explore the roles of the functional SNPs in ABO gene on transcriptional regulation. Our results will provide a method to screen the high-risk groups and susceptible individuals for the large artery atherosclerotic stroke. And show important academic values for predicting of disease development and clarifying the pathogenesis of disease.

脑卒中是世界范围内第一位成人致残原因和第二位致死原因，约70％～80％脑卒中是缺血性脑卒中（脑梗死），大动脉粥样硬化性脑梗死是脑梗死的主要类型，近期的一项大规模的欧洲人群的全基因组关联研究发现位于ABO基因的一个SNP位点（rs505922）与大动脉粥样硬化性脑梗死相关。但关联的具体机制尚不明确，流行病学调查发现，ABO基因存在明显的地区和人种差异。因此，本课题在前期研究基础上，对ABO基因进行精细作图，分析该基因多态性与中国汉族人群大动脉粥样硬化性脑梗死发生和预后的关系，评价基因-基因和基因-环境交互作用，建立大动脉粥样硬化性脑梗死的多因素预测模型，同时探讨功能性SNPs对ABO基因转录调控的影响。研究结果对明确大动脉粥样硬化性脑梗死高危人群、预测疾病发展进程、深入阐释发病机制将具有重要意义和学术价值。

脑卒中是世界范围内第一位成人致残原因和第二位致死原因，约70％～80％脑卒中是.缺血性脑卒中（脑梗死），大动脉粥样硬化性脑梗死是脑梗死的主要类型，近期的一项大规模的欧洲人群的全基因组关联研究发现位于ABO基因的一个SNP位点（rs505922）与大动脉粥样硬化性脑梗死相关。但关联的具体机制尚不明确，流行病学调查发现，ABO基因存在明显的地区和人种差异。因此，本课题在前期研究基础上，对ABO基因进行精细作图，分析该基因多态性与中国汉族人群大动脉粥样硬化性脑梗死发生和预后的关系，评价基因-基因和基因-环境交互作用，建立大动脉粥样硬化性脑梗死的多因素预测模型，同时探讨功能性SNPs对ABO基因转录调控的影响。研究发现在中国汉族人群中，ABO基因遗传变异和LAA脑梗死的发病有关。采用MDR分析，研究未发现10个SNP之间存在明显交互作用。rs505922 CC等位基因可能是LAA脑梗死复发的一个危险因素，rs505922可能与LAA脑梗死的死亡无明显相关性。研究结果对明确大动脉粥样硬化性脑梗死高危人群、预测疾病发展进程、深入阐释发病机制将具有重要意义和学术价值。