染色体11q23.3单核苷酸多态性与中国汉族人群心肌梗死的相关性研究

发布时间：2018-05-30 08:46

本文选题：心肌梗死 + 单核苷酸多态性　；参考：《吉林大学》2015年博士论文

【摘要】：心肌梗死是冠状动脉粥样硬化性心脏病进展到后期的一种严重疾病，心肌梗死是由多种环境因素和多种遗传因素共同参与作用所造成的一种复杂的疾病。单核苷酸多态性与心肌梗死的相关性研究是心肌梗死病因和发病机理遗传学研究方面的重要内容，而由于在种族的迁徙和进化过种中，基因重组不断的发生，因此，单核苷酸多态性与疾病的相关性在不同种族之间经常存在不一致性。目的：研究证实部分在非中国人群中报道的和心肌梗死或冠心病存在相关性的单核苷酸多态性在中国汉族人群是否和心肌梗死存在相关性，为全球多种族范围内心肌梗死易感性标志物的筛选，以及心肌梗死遗传学方面的机理研究提供部分理论数据依据。方法：按照预先设定的入选标准，我们共入选了549例中国汉族急性心肌梗死的患者，入选了551例中国汉族既往无冠状动脉粥样硬化性心脏病病史者作为对照组。采用问卷调查和临床住院病历资料收集相结合的方式来收集所有研究样本的资料。所有标本采集外周静脉血，应用酚-氯仿法提取全基因组DNA。按照预先设定的入选标准，我们随机入选了三个在非中国人群中报道的和心肌梗死或冠心病存在相关性的单核苷酸多态性作为我们的研究对象，这三个单核苷酸多态性分别是rs1412444(LIPA)，rs662799(APOA5)和rs964184(ZNF259)，我们对每个标本的基因组DNA，应用基因测序的方法对这三个单核苷酸多态性的基因型进行检测，再结合每个标本的临床资料，我们应用SNPStats软件进行统计学分析，并对混杂风险因素进行校正，以及应用Bonferroni校正方法来校正单核苷酸多态性选择过程中出现的偏倚。结果：研究结果显示在中国汉族人群单核苷酸多态性rs662799与心肌梗死显著性相关，经过混杂风险因素校正及Bonferroni校正后，在遗传模型意义相对较大的相加模型中，其比值比为1.39，其比值比的95%可信区间为1.09-1.78，p值为0.0228；在中国汉族人群单核苷酸多态性rs964184亦与心肌梗死显著性相关，经过混杂风险因素校正及Bonferroni校正后，在遗传模型意义相对较大的相加模型中，其比值比为1.52，其比值比的95%可信区间为1.16-1.98，p值为0.0060；然而，在中国汉族人群单核苷酸多态性rs1412444却并未发现与心肌梗死存在相关性，经过混杂风险因素校正及Bonferroni校正后，在遗传模型意义相对较大的相加模型中，其比值比为1.11，其比值比的95%可信区间为0.87-1.40，p值为1.0000。对和心肌梗死相关的两个单核苷酸多态性rs662799和rs964184进行连锁不平衡分析发现它们二者存在连锁不平衡：心肌梗死组为：D’=0.959，r2=0.652；对照组为：D’=0.955，r2=0.658。进一步的单体型分析发现单核苷酸多态性rs662799和rs964184组成的GG单体型与心肌梗死存在显著相关性，经过混杂风险因素校正及Bonferroni校正后，在遗传模型意义相对较大的相加模型中，其比值比为1.50，95%可信区间为1.14-1.97，p值为0.0034。为进一步探讨我们所研究的单核苷酸多态性与心肌梗死相关性可能存在的有关机制，我们对部分混杂风险因素的与我们研究的单核苷酸多态性进行统计学上的二次分析。结果发现，在中国汉族人群单核苷酸多态性rs662799与甘油三脂显著性相关，，经过混杂风险因素校正及Bonferroni校正后，在遗传模型意义相对较大的相加模型中，其差异为0.09，其差异的95%可信区间为0.04-0.14，p值=0.0015；在中国汉族人群单核苷酸多态性rs964184亦与甘油三脂显著相关，经过混杂风险因素校正及Bonferroni校正后，在遗传模型意义相对较大的相加模型中，其差异为0.07，其差异的95%可信区间为0.01-0.12，p值=0.042；而在中国汉族人群单核苷酸多态性rs1412444却并未发现与甘油三脂存在相关性，经过混杂风险因素校正及Bonferroni校正后，在遗传模型意义相对较大的相加模型中，其差异为-0.04，其差异的95%可信区间为-0.08-0.01，p值=0.48。结论：本研究结果表明，位于染色体11q23.3上的两个单核苷酸多态性rs964184和rs662799在中国汉族人群与心肌梗死存在显著的相关性，其相关的致病基因可能与甘油三脂相关；而位于染色体10q23上的单核苷酸多态性rs1412444在中国汉族人群未发现与心肌梗死存在相关性。而这三个单核苷酸多态性既往在非中国汉族人群的其他种族人群中均曾报导和心肌梗死或冠心病有关，其结果进一步表明单核苷酸多态性与疾病的相关性在不同种族存在差异。本研究为中国汉族人群心肌梗死在遗传学研究领域完善了部分数据，可给未来在全球多种族内研究心肌梗死易感性标志物筛选，以及心肌梗死遗传学方面的机理研究提供部分数据的理论依据。
[Abstract]:Myocardial infarction is a serious disease in the late stage of coronary atherosclerotic heart disease . Myocardial infarction is a complex disease caused by multiple environmental factors and multiple genetic factors . The correlation between single nucleotide polymorphism and myocardial infarction is an important element in the pathogenesis and pathogenesis of myocardial infarction .

Objective : To study whether single nucleotide polymorphism ( SNPs ) associated with myocardial infarction or coronary heart disease ( AMI ) and myocardial infarction ( AMI ) in non - Chinese population is associated with myocardial infarction , and provides some theoretical data for the screening of susceptibility markers for myocardial infarction within the global multiracial range , as well as the mechanism of myocardial infarction genetics .

Methods : A total of 549 Chinese Han Chinese patients with acute myocardial infarction were enrolled and 551 Chinese Han Chinese were selected as control group . All the samples were collected from peripheral venous blood and the whole genomic DNA was extracted by phenol - chloroform method . According to the pre - set inclusion criteria , we randomly selected three single nucleotide polymorphisms ( rs1412444 ( LIPA ) , rs662799 ( APOA5 ) and rs964184 ( ZNF259 ) .

Results : The results showed that the single nucleotide polymorphism rs662799 of Chinese Han population was significantly correlated with myocardial infarction , and the odds ratio was 1 . 39 , the 95 % confidence interval of the odds ratio was 1.09 - 1.78 , and the p - value was 0.0228 .
The single nucleotide polymorphism rs964184 of Chinese Han population was also significantly correlated with myocardial infarction . After confounding risk factor correction and Bondevii correction , the odds ratio was 1.52 , the 95 % confidence interval of the odds ratio was 1.16 - 1.98 , p - value was 0.0060 ;
However , the single nucleotide polymorphism rs1412444 in Chinese Han population did not find a correlation with myocardial infarction , and the odds ratio was 1.11 , with a 95 % confidence interval of 0.87 - 1.40 and a p - value of 1.0000 . The linkage disequilibrium between the two single nucleotide polymorphisms rs662799 and rs964184 associated with myocardial infarction showed linkage disequilibrium : D ' = 0.959 , r2 = 0.652 ;
There was a significant correlation between single nucleotide polymorphism rs662799 and rs964184 in the control group . There was a significant correlation between single nucleotide polymorphism rs662799 and rs964184 . The odds ratio was 1.50 , 95 % confidence interval 1.14 - 1.97 , p - value 0.0034 .

In order to further explore the possible mechanism of single nucleotide polymorphism and myocardial infarction in Chinese Han population , we statistically analyzed some confounding risk factors and the single nucleotide polymorphism we studied . The results showed that the difference of single nucleotide polymorphism rs662799 and triglyceride in Chinese Han population was 0.09 , the 95 % confidence interval of the difference was 0.04 - 0.14 , p - value = 0.0015 ;
The single nucleotide polymorphism rs964184 of Chinese Han population was also significantly correlated with triglyceride , after confounding risk factor correction and Bondevii correction , the difference was 0.07 , the 95 % confidence interval of the difference was 0.01 - 0.12 , p - value = 0.042 ;
However , the single nucleotide polymorphism rs1412444 of Chinese Han population did not find a correlation with triglyceride , after confounding risk factor correction and Bondevii correction , the difference was - 0.04 , the 95 % confidence interval of the difference was - 0.08 - 0.01 , p - value = 0.48 .

Conclusion : Two single nucleotide polymorphisms rs964184 and rs662799 located on chromosome 11q23 have a significant correlation with myocardial infarction in Chinese Han population .
The single nucleotide polymorphism rs1412444 , which is located on chromosome 10q23 , has not been found to be associated with myocardial infarction in Chinese Han population . These three single nucleotide polymorphisms have previously been reported in other ethnic groups in the Han population in China . The results suggest that the correlation between single nucleotide polymorphism and disease is different in different races .
【学位授予单位】：吉林大学
【学位级别】：博士
【学位授予年份】：2015
【分类号】：R542.22

【共引文献】