【作者】 冯涛；

【导师】 吴卫平；

【作者基本信息】 中国人民解放军军医进修学院 ， 神经病学， 2009， 博士

【摘要】 目的:研究C反应蛋白启动子区-717A/G基因多态性与C反应蛋白水平及脑梗死的关系。方法:选择脑梗死病例125例及正常对照组130例,测定身高、体重、收缩压、舒张压、空腹血糖、C反应蛋白、红细胞压积、血小板数、血小板体积、凝血酶原时间、凝血酶原活动度、活化部分凝血酶原时间、凝血酶时间、纤维蛋白原、甘油三脂、胆固醇、低密度脂蛋白、高密度脂蛋白等生化指标。用外周血提取DNA,采用PCR-RFLP方法确定启动子区-717A/G基因型及其多态性。利用χ~2检验对脑梗死病例组及正常对照组间基因型、等位基因频率比较。对所有个体颈动脉内膜中层厚度分组,对脑梗死病例组按梗死灶大小分组,并对脑梗死病例组按NIHSS评分分组。采用χ~2检验,分别对每种分组的不同组别进行等位基因频率比较。以比值比(OR)及95%可信区间(CI)表示各种基因型、等位基因与疾病风险的相关性,P＜0.05为差异有显著意义。应用SAS9.1.3统计软件,计算均数,标准差,百分率等,对计量资料的AA、AG、GG各基因型间的比较进行单因素方差分析,采用logistic回归分析筛选对脑梗死的主要危险因素。结果:病例组等位基因A的频率为0.84,对照组A的频率为0.79,病例组等位基因A的频率要高于对照组,但无统计学意义。对所有个体颈动脉内膜中层厚度分组,启动子区-717A/G等位基因频率与颈动脉内膜中层厚度差异无统计学意义。对脑梗死病例组按梗死灶大小分组,并对脑梗死病例组按NIHSS评分分组,启动子-717A/G等位基因频率与梗死灶大小差异有统计学意义,A等位基因在小灶梗死中的频率明显低于中灶梗死和大灶梗死;同时,启动子区-717A/G等位基因频率与NIHSS评分分组差异有统计学意义,A等位基因在轻型组中的频率明显低于重型组。我们又发现,含有从型与AG型个体的血清CRP水平明显高于GG型个体。这说明等位基因A可能有增加C反应蛋白水平的趋势。病例组胆固醇、甘油三酯、血糖、C反应蛋白、纤维蛋白原、收缩压明显高于对照组。通过逻辑回归分析,与脑梗死相关性作用由大到小分别是:C反应蛋白,胆固醇,血糖,纤维蛋白原,年龄,收缩压。结论:以上研究表明,位点-717A/G可能与脑梗死的程度和病情的严重性相关。等位基因A在发生大面积脑梗死的患者中频率较高。另外,C反应蛋白、胆固醇、血糖、纤维蛋白原、年龄、收缩压等因素对脑梗死的有直接作用。更多还原

【Abstract】 Objective:To study the relationships between the -717A/G functional polymorphism of C-reactive protein promoter with C-reactive protein level and cerebral infarction.Methods:In this study,125 cerebral infarction cases and 130 control cases were recruited.The following parameters were measured:height,weight,systolic blood pressure,diastolic blood pressure,fasting blood glucose,C-reactive protein, hematocrit,platelet count,platelet volume,prothrombin time,prothrombin activity,activated partial prothrombin time,thrombin time,fibrinogen, triglyceride,cholesterol,low density lipoprotein and high density lipoprotein. DNA was extracted from peripheral blood.PCR was employed afterwards for amplification.We genotyped the -717A/G locus by PCR-RFLP method.Statistical analysis was performed by Pearson’s chi-square test and SPSS software was utilized for the allele and genotype association analysis.Logistic regression analysis was employed to identify the main causes of cerebral infarction.Results:The frequency of allele A was higher in the case group than that in the control group.Statistical analysis showed that -717A/G was not associated with cerebral infarction and the inteima-media thickness for the whole samples. However,-717A was associated with the middle and big size infarction region compared with the small one.In the case group of cerebral infarction,a statistically significant difference in the distribution of the -717A allele between mild and severe patients according to NIHSS scores was also observed.In addition,the average level of C-reactive protein was higher in the AA and AG genotypic subjects than that in the GG genotypic subjects.The levels of Cholesterol,Triglycerides,Blood glucose,C-reactive protein,Fibrinogen,Systolic blood pressure were much higher in the patient group than it in the control group.By using logistic regression analysis,researchers also identified the following cerebral infarction inducing factors,which were ranked by the degree of correlation:C-reactive protein, Cholesterol,Blood glucose,Fibrinogen,Age and Systolic blood pressure.Conclusions:There is significant relationship between the-717A/G functional polymorphism of C-reactive protein promoter with C-reactive protein level and the cerebral infarction,and -717A allele may be associated with severe cerebral infarction.C-reactive protein,Cholesterol,Fibrinogen,Blood glucose,Age and Systolic blood pressure are all risk factors of the cerebral infarction disease.更多还原