Abstract: Objective Ischemic stroke(IS) is a multi-genes disease and closely related to the genetic factors. Genome-wide association studies(GWAS) which have single nucleotide polymorphisms(SNP) for the genetic markers system found that chromosome 9p21 polymorphism is an independent atherosclerotic risk factor, and associated to the susceptibility to atherosclerotic IS. However, due to the small sample size, there is no significant differences between the case group and the control group through comparing the allele frequency distribution, which highlights the need for larger-scale study. This study is to confirm the association between SNP type of chromosome 9p21 and the susceptibility to atherosclerotic IS by doing meta-analysis on all related published data after strict quality control, and to evaluate its risk of the disease.Methods We searched all the case-control studies referring to the association between chromosome 9p21 polymorphisms and atherosclerotic IS and formulated strict inclusive and exclusive quality control criteria. And we used the special software RevMan5.0 which provided by internationalCochrane Collaboration to do mete-analysis on the data. RevMan5.0 shows the odds ratio(OR) value and 95% confidence interval(CI) of each study and the combined statistical OR value and 95%CI by the forest plots. To evaluate the different frequency distribution of SNPs of chromosome 9p21 which confer risk of atherosclerotic IS between the cases and the controls systematically, and to analyze statistical significance of the association between Chromosome 9p21 polymorphisms and atherosclerotic IS.Results Meta-analysis included six multi-centers clinical case-control studies which across Europe and North America. Meta-analysis selected seven SNPs of chromosome 9p21:rs7044859, rs496892,rs564398, rs7865618, rs1537378, rs2383207, rs10757278. Five SNPs:rs564398, rs7865618, rs1537378,rs2383207, rs10757278 have statistically significant correlation with atherosclerotic IS and confer risk of the susceptibility to atherosclerotic IS. While neither rs7044859 nor rs496892 has.Conclusion The study discovered five SNPs(rs564398, rs7865618, rs1537378, rs2383207, rs10757278) of chromosome 9p21 associated to the susceptibility to atherosclerotic IS. Variants on chromosome 9p21 are considered to be an independent atherosclerotic risk factor and the candidate gene of atherosclerotic IS.

Key words: Ischaemic stroke; Atherosclerotic; Single nucleotide; polymorphism; Meta-analysis

摘要： 目的 缺血性卒中（ischaemic stroke，IS）是一种与遗传因素密切相关的多基因疾病。以单核苷酸多态性（single nucleotide polymorphism，SNP）为遗传标记系统的全基因组关联研究（Genomewide Association Studies，GWAS）发现染色体9p21多态性是血管粥样硬化的独立危险因素，与动脉粥样硬化性缺血性卒中易感风险相关；但由于样本量较小，通过比较等位基因频率分布，显示其在病例组与对照组之间无明显差异，这突出了更大规模研究的必要性。本研究拟对目前已发表的有关染色体9p21多态性与动脉粥样硬化性缺血性卒中易感相关性的病例-对照研究严格质量控制后进行Meta分析，旨在明确染色体9p21与动脉粥样硬化性缺血性卒中易感相关性的SNP种类，并对其与疾病发生风险的大小进行评估。方法 联合检索目前已发表的全部有关染色体9p21多态性与动脉粥样硬化性缺血性卒中易感相关性的病例-对照研究，制定严格的纳入排除质量控制标准，应用国际Cochrane系统评价协作网提供的Meta分析专用软件RevMan5.0对数据进行Meta分析，用森林图（Forest Plot）展示各个研究的OR（odds ratio）值及95％可信区间（confidence interval，CI）以及合并统计的OR值及95%CI，系统评价染色体9p21与动脉粥样硬化性缺血性卒中易感相关性的SNP在病例组与对照组分布有无差异，分析得到染色体9p21多态性与动脉粥样硬化性缺血性卒中易感相关性的统计学意义。结果 进入Meta分析的资料涉及6项跨越欧洲与北美洲的多中心临床病例-对照研究。进入Meta分析的基因多态性涉及染色体9p21上的7种SNP：rs7044859、rs496892、rs564398、rs7865618、rs1537378、rs2383207及rs10757278。其中，rs564398、rs7865618、rs1537378、rs2383207和rs10757278与动脉粥样硬化性缺血性卒中相关性具有统计学意义，与动脉粥样硬化性缺血性卒中易感风险相关。而rs7044859、rs496892与动脉粥样硬化性缺血性卒中相关性无统计学意义。结论 本研究发现染色体9p21的5种SNP（rs564398、rs7865618、rs1537378、rs2383207及rs10757278）与动脉粥样硬化性缺血性卒中具有易感相关性，染色体9p21变异被认为是血管粥样硬化的危险因素，是动脉粥样硬化性缺血性卒中的候选易感基因。

关键词: 缺血性卒中; 动脉粥样硬化; 单核苷酸; 多态性; Meta分析