【作者】 刘娜；

【导师】 资晓宏；

【作者基本信息】 中南大学 ， 临床医学， 2013， 博士

【摘要】 目的探讨胶原基因(COL3A1、COL1A2)单核苷酸多态性与脑梗死及动脉粥样硬化斑块的相关性。方法采用病例对照研究设计,严格按准入及排除标准收集湘雅三医院住院脑梗死患者作为脑梗死组,并根据颈动脉彩超检查结果分为稳定斑块组和易损斑块组两个亚组,另选年龄和性别与脑梗死组匹配的健康者作为对照组,各研究对象之间无任何血缘关系。详细询问各研究对象的病史并记录其检查检验结果,抽取其清晨空腹静脉血,采用DNA提取试剂盒提取基因组DNA,运用聚合酶链反应-限制性酶切片段长度多态性(PCR-RFLP)方法检测研究对象COL3A1基因rs1800255位点及COL1A2基因rs42524位点多态性,分析其与脑梗死、颈动脉内膜中层厚度(CIMT)、颈动脉斑块类型的相关性。结果1. COL3A1基因rsl800255位点各基因型在脑梗死组和对照组之间的分布有显著性差异(P<0.05),A等位基因携带者(AA+AG)与GG基因型者在脑梗死组和对照组之间分布有显著性差异(P<0.05),但是A、G等位基因频率在两组间分布无显著性差异(P>0.05),经过二元非条件logistic回归分析未发现该位点任何一种基因型能增加或减少脑梗死的发病风险(P>0.05)；2. COL3A1基因rsl800255位点各基因型和等位基因频率在不同CIMT水平的分布无显著性差异(P>0.05)：3. COL3A1基因rs1800255位点各基因型及基因频率在脑梗塞不同斑块性质亚组及对照组间分布有显著性差异(P<0.05),且logistic回归分析发现该位点AA基因型使易损斑块发生风险增加(P<0.05)；4. COL1A2基因rs42524位点各基因型和等位基因频率在脑梗死组和对照组之间分布无显著性差异(P>0.05),且二元非条件logistic回归分析未发现任何该位点一种基因型能增加或减少脑梗死发生的风险(P>0.05)；5. COL1A2基因rs42524位点各基因型和等位基因频率在不同CIMT水平的分布无显著性差异(P>0.05)；6. COL1A2基因rs42524位点各基因型和等位基因频率在脑梗死稳定斑块亚组和易损斑块亚组及对照组间的分布不存在统计学差异(P>0.05),二元非条件logistic回归分析未发现该位点任一种基因型增加或减少易损斑块的发生风险(P>0.05)。结论1.COL3A1基因rs1800255多态性与中国湖南地区汉族人群中脑梗死的发病相关,脑梗死发病可能与rs1800255位点AA/AG基因型有关,但rs1800255多态性不是脑梗死发生的独立危险因素,rs1800255位点多态性与颈动脉内膜中层厚度水平不相关,rs1800255位点AA基因型可能是颈动脉易损斑块发生的一个危险因素；2. COL1A2基因rs42524多态性与中国湖南地区汉族人群中脑梗死的发病不相关,rs42524多态性与颈动脉内膜中层厚度水平不相关,rs42524位点多态性与颈动脉易损斑块的发生风险无关。更多还原

【Abstract】 Objective To clarify the suspended association of the collagen gene(COL3A1, COLlA2) polymorphisms with cerebral infarction and to discuss the relationship between polymorphisms of collagen gene and onset risk of atherosclerotic plaque.Methods Case control study was performed in this study. We collected cerebral infarction patients as CI group, which was divided into stable plaque subgroup and vulnerable subgroup according to carotid ultrasound examination. Then we chose healthy individuals as the control group,whose ages and sexes were matched with the CI group. There were no relationships among the subjects. We collected the case history and recorded the examination results seriously. We draw fasting venous blood from every subject early in the morning and obtained DNA from the blood sample using Blood DNA Kit. PCR-RFLP was used to detect the polymorphisms of COL3A1-SNP-rs1800255and COLlA2-SNP-rs42524of all subjects. Association of the collagen gene (rs1800255, rs42524) polymorphisms with cerebral infarction, carotid intima-media thickness and onset risk of carotid stable plaque, vulnerable plaque was analyzed.Results1.The genotypic distribution of rs1800255had significant differences between the CI group and the control group (P<0.05), and had significant differences between the A allele (AA+AG) carriers and the GG genetype carriers for rs1800255(P<0.05), but the allelic distributions of rs1800255had no significant differences between the CI group and the control group (P>0.05). Logistic regression analysis showed that any genotypes of rs1800255could not increase the risk of the onset of CI (P>0.05).2.The genotypic and allelic distributions of rs1800255had no significant differences between different CIMT level subgroups (P>0.05).3.The genetypic and allelic distribution of rs1800255had significant differences between the stable plaque, vunerable plaque subgroups and the control group (P<0.05). Logistic regression analysis showed that AA genotype could increase the risk of the onset of vunerable plaque (P<0.05).4.The genotypic and allelic distribution of rs42524had no significant differences between the CI group and the control group (P>0.05). Logistic regression analysis showed that any genotypes of rs42524could not increase the risk of the onset of CI (P>0.05).5.The genotypic and allelic distributions of rs42524had no significant differences between different CIMT level subgroups (P>0.05).6.The genetypic and allelic distribution of rs42524had no significant differences between the vunerable plaque, stable plaque and control groups (P>0.05). Logistic regression analysis showed that any genotypes of rs42524could not increase the risk of the onset of vunerable plaque (P>0.05).Conclusion1. Association of rs1800255polymorphisms with cerebral infarction in Hunan Han Population may exit. AA/AG genotype of rs1800255may play promoting actor for the onset of cerebral infarction, but it is not an independent risk factor for the onset of cerebral infarction. No association of rs1800255polymorphisms with CIMT levels exists. The AA genetype of the rs180255may be a risk factor for the formation of carotid vulnerable plaque in Hunan Han Population.2. Association of the rs42524polymorphisms with cerebral infarction in Hunan Han Population may not exist. No association of rs42524polymorphisms with CIMT levels exists. The polymorphism of rs42524has nothing to do with onset risk of carotid stable plaque or vulnerable plaque.更多还原