关键词: 缺血性卒中; 动脉粥样硬化; 单核苷酸; 多态性; Meta分析

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