【作者】 刘靖；

【导师】 陈吉相；

【作者基本信息】 华中科技大学 ， 神经病学， 2017， 硕士

【摘要】 目的:卒中已经成为中国人最主要的死亡原因。缺血性卒中（脑梗塞,IS）占所有卒中的77.8%。在我国,大动脉粥样硬化是IS发生的主要原因。研究表明,IS是由基因和环境因素相互作用引起的复杂综合征。目前,国内外一些全基因组关联分析（GWAS）发现了与IS及其各亚型相关的部分风险位点,但是关于这些风险位点的研究结论不尽相同,且鲜有研究报道不同民族之间易感性的差异。为了验证国内外研究中发现的基因位点是否与汉族和哈萨克族人群IS,特别是大动脉粥样硬化型脑梗塞（LAA）的易感性相关,我们设计了此项研究。方法:本研究采用病例-对照研究方法,选取2015-2017年武汉协和医院神经内科住院部101例汉族IS患者及新疆博州人民医院神经内科住院部54例哈萨克族IS患者作为IS组,并随机选取两个医院的无脑血管病人群（分别为36例和17例）作为对照组。根据TOSAT（the Trial of Org 10172 in Acute Stroke Treatment）分型,进一步将IS组分为LAA组和非LAA组。留取试验对象静脉血,提取基因组DNA,采用SNP shot方法对与IS有关的12个位点进行分析。将各组各个突变位点基因频率用SPSS 22.0软件进行统计学分析。结果:1、汉族人群中,LAA组与对照组比较,rs2383207基因型频率有统计学差异(p=0.043,其中,OR_（G/A）=0.337,p=0.014),但等位基因频率无统计学差异。而IS组与对照组比较,所有位点基因型和等位基因频率均无统计学差异。2、哈族人群中,rs10757278基因型频率在IS组和对照组中有统计学差异(p=0.003,其中,OR_（G/A）=0.150,p=0.002),但等位基因频率无统计学差异。3、汉族与哈族IS组比较,相较于哈族,汉族rs2383207的基因型频率(p=0.047其中,OR_（G/A）=0.444,p=0.024)和等位基因频率(p=0.015,其中,OR_（A）=0.545,p=0.015)差别均有统计学意义。rs2383207的基因型频率（p=0.047）和等位基因频率（p=0.015）差别均有统计学意义。4、根据不同遗传模式的比较,汉族人群中,IS组与对照组比较,所有位点的各种遗传模式均无统计学差异。LAA组与对照组比较,rs2383207的共显性模式的GA基因型（p=0.014）和显性模式有统计学差异（p=0.028）。哈族人群中,IS组与对照组比较,rs10757278的共显性模式中的GA基因型（p=0.002）和显性模式（p=0.022）有统计学差异。结论:1、rs2383207-GA可能会降低汉族人群LAA的发生风险。2、rs10757278-GA可能会降低哈族人群IS的发生风险。3、汉族与哈族IS组比较,相较哈族人群,rs2383207的GA基因型和A等位基因可能会降低汉族人群IS的发生风险。4、rs2383207-A携带可能会降低汉族人群LAA的发生风险。rs10757278-G携带可能会降低哈萨克族人群IS的发生风险。更多还原

【Abstract】 Objective:In China,stroke has ranked the first of mortality in recent decades.The ischemic strokes（IS）,also termed as cerebral infarctions,account for 77.8%of strokes.In our country,the large-artery atherosclerosis is the main reason of IS.Researches have demonstrated that IS is more a multifactorial disorder than a single factor disease.At present,genome-wide association studies（GWAS）have been conducted at home and abroad to propose that some SNPs contribute to IS,as well as its subtypes.However,no consistent results have reached and rare studies have reported the difference of susceptibility between different nationalities.We designed this study in order to verify whether genetic loci reported at home and abroad should be responsible for IS,especially for large-artery atherosclerosis strokes（LAA）in Han and Kazak nationalities.Methods:A case-control study was adopted from the year 2015 to 2017.A total of 101 Han nationality IS patients and 54 Kazark nationality IS patients were recruited from the in in-patient settings of department of Neurology,Union Hospital in Wuhan and People’s Hospital of Bozhou in Sinkiang.36 subjects in Wuhan and 17 in Bozhou who were free from cerebrovascular diseases were selected as control group.Additionally,group assignments were made via TOAST（the Trial of Org 10172 in Acute Stroke Treatment）to divide IS group into the LAA and non-LAA groups.The venous blood was obtained to extract genomic DNA.SNP shot was adopted to analyze the 12 loci relating to IS.The frequency of genotypes and alleles were analyzed by SPSS22.0 software.Results:1.In Han Nationality groups,compared with the controls,there was statistical significance between rs2383207 and LAA in frequency of genotype(p=0.043,with OR_（G/A）=0.337,p=0.014),while no statistical significance was found in frequency of allele.Neither did frequencies in genotype or allele in IS group.2.In Kazak Nationality groups,only rs10757278 reached statistical significance in frequency of genotype with IS(p=0.003,with OR_（G/A）=0.150,p=0.002),while no statistical significance was found in frequency of allele.3.Compared with Kazak nationality IS group,Han nationality IS group reached statistical significance both in frequency of genotype(p=0.047,with OR_（G/A）=0.444,p=0.024)and allele(p=0.015,with OR_（A）=0.545,p=0.015)in locus rs2383207.4.According to genetic model assignments,no statistical difference was found in IS groups of Han nationality.Locus rs2383207 under the GA genotype of co-dominant（p=0.014）and dominant model（p=0.028）reached statistical significance in LAA group.As to Kazak Nationality groups,the GA genotype of co-dominant（p=0.002）and dominant model（p=0.022）in locus rs10757278 were statistically different in IS groups.Conclusion:1.rs2383207-GA may be associated with decreased risk of LAA in Han population.2.rs10757278-GA may be associated with decreased risk of IS in Kazak population.3.Compared with Kazak nationality IS group,rs2383207-GA and rs2383207-A may be associated with decreased risk of IS in Han nationality.4.rs2383207-A may be associated with decreased risk of LAA in Han population.In addition,rs10757278-G may be associated with decreased risk of IS in Kazak population.更多还原