【作者】 陈多学；

【导师】 王爱玲； 余元勋；

【作者基本信息】 安徽医科大学 ， 内科学， 2010， 硕士

【摘要】 研究目的:肥厚型心肌病是一种以非对称性心肌肥厚为特征的常染色体显性遗传病。遗传异质性和外显率不全使肥厚型心肌病的基因型和表型关系变得复杂化,有关血管紧张素原基因(AGT)M235T多态性影响肥厚型心肌病基因型和表型相互关系的研究较多,但是在国内外不同的人群中得出的研究结果却并不一致,有的认为血管紧张素原基因(AGT)M235T可以影响肥厚型心肌病基因型和表型相互关系,有的则认为没有影响。国内有研究发现AGTM235T可以影响肥厚型心肌病基因型和表现型相互关系,本文拟在安徽省的人群中研究血管紧张素原基因(AGT)M235T多态性与肥厚型心肌病的相关性,左室流出道梗阻作为肥厚型心肌病的一个常见而重要的表现型,故本文又着重研究了伴随有左室流出道梗阻的肥厚型心肌病患者与血管紧张素原基因(AGT)M235T多态性的相关性,以探讨影响肥厚型心肌病外显率不全的影响因素。研究对象和方法:收集近5年来我省肥厚型心肌病患者共94例,所有患者均行超声心动图检查确诊为肥厚型心肌病。同时收集120例健康对照者作为对照组,排除肥厚型心肌病,同时排除可能存在血管紧张素原基因(AGT)M235T多态性异常的高血压病、冠心病、缺血性脑血管病等。用PCR技术和直接测序法,检测94名肥厚型心肌病患者和120名对照者血管紧张素原基因(AGT)M235T多态性。数据用均数±标准差表示,应用SPSS10.0统计软件进行统计学分析,采用卡方检验进行基因型分布和等位基因频率及Hardy-Weinberg平衡检验,组间表型比较用多元回归分析,P<0.05为有显著性差异。研究结果:肥厚型心肌病患者组和对照组的基因型构成比和等位基因频率相互比较,差异没有显著性(χ2=0.29,0.24,P > 0.05),梗阻性和非梗阻性肥厚型心肌病患者亚组之间的基因型构成比和等位基因频率相互比较,差异也没有显著性(χ2=0.28,0.15,P > 0.05)。结论:血管紧张素原基因(AGT)M235T多态性与肥厚型心肌病的发病和是否有左室流出道梗阻无关,血管紧张素原基因(AGT)M235T多态性可能不是肥厚型心肌病外显率不全的影响因素。更多还原

【Abstract】 Objective: Hypertrophic cardiomyopathy is a primary autosomal dominant inheritant myocardial disorder characterized by asymmetric myocardial hypertrophy. Genetic heterogeneity and expressivity diffrence make the relationship between genotypes and phenotypes of hypertrophic cardiomyopathy complex. There are many studies about angiotensinogen gene (AGT) M235T polymorphism whether effect the relationship between the genotypes and phenotypes in hypertrophic cardiomyopathy patients worldwildly with inconsistent results, some studies found it maybe effect the relationship, while some studies found not. In a population of Anhui , we investigate the relationship between AGTM235T polymorphism and hypertrophic cardiomyopathy, especially the relationship between AGT M235T polymorphism and hypertrophic cardiomyopathy patients with left ventricular outflow tract obstruction which is a common and important phenotype. and discuss the factor which maybe effect the the expressivity diffrence in hypertrophic cardiomyopathy.Methods: A total of 94 hypertrophic cardiomyopathy patients in a population of Anhui were enrolled in the last five years diagnosed on the basis of echocardiographic criteria. And a total of 120 normal controls were enrolled at the same time without hypertrophic cardiomyopathy, and also without disorders that maybe assotionated with angiotensinogen gene M235T polymorphism such as hypertension, coronary atherosclerotic heart disease, and ischemic cerebrovascular disease. Polymerase chain reaction and sequencing directly were used to detect AGTM235T polymorphism of 94 hypertrophic cardiomyopathy patients and 120 normal controls. Data are expressed as means±standard deviation. Statistical analysis was performed with the SPSS 10.0 package. Chi-square test was used to test for genotype distribution and allele frequency and Hardy-Weinberg equilibrium of the polymorphisms. Multiple regression analysis was conducted for multiple genotypes between the two groups . A value of P<0.05 was considered significant.Results: The contribution of the genotype and the frequency allele of the AGTM235T polymorphism had no difference significantly in hypertrophic cardiomyopathy patient group and the control group(χ2= 0.29, 0.24, P >0.05). And those also had no difference significantly in hypertrophic cardiomyopathy subgroups regardless of there are left ventricular outflow tract obstruction or not(χ2=0.28, 0.15, P>0.05).Conclusions: AGTM235T polymorphism is not significantly associated with hypertrophic cardiomyopathy and left ventricular outflow tract obstruction. AGT M235T polymorphism maybe is not the modification gene which effect the expressivety diffrence in hypertrophic cardiomyopathy.更多还原