ApoE基因启动子区DNA甲基化与动脉粥样硬化性脑梗死的关系
发布时间：2018-08-02 09:03
【摘要】：背景人类的载脂蛋白E(ApoE)基因是肝清除残余脂蛋白的一个关键基因,一种抗动脉粥样硬化的重要基因。载脂蛋白E(ApoE)基因及其蛋白(ApoE)在脂质代谢中发挥关键作用,包括脂蛋白和胆固醇的再分配。Apo E分为三个常见的亚型:E2、E3和E4,分别被ε2、ε3和ε4三个等位基因编码。大量人群调查发现ε4等位基因可以显著地升高健康人的总胆固醇水平,使携带者易患动脉粥样硬化;相反,ε2等位基因可以降低携带者的胆固醇水平,而且其降低胆固醇的效应是ε4升高胆固醇效应的2~3倍。此外,ApoE基因的ε2、ε3和ε4等位基因也与家族性和散发性阿尔茨海默病(AD)有关。随着社会的老龄化,脑梗死的发病率逐年上升,其中,动脉粥样硬化性脑梗死最为常见,约占全部脑梗死的60%,是本研究的关注点。脑梗死是一种多基因遗传疾病,是遗传和环境相互作用的结果,表观遗传学为其研究提供了新思路。表观遗传学是基因序列不变,基因表达发生可遗传的改变,主要包括DNA甲基化、组蛋白修饰、染色质重塑、非编码RNA调控等,目前研究较为深入的是DNA甲基化。基于以上,本实验旨在探索ApoE基因启动子区DNA甲基化与动脉粥样硬化性脑梗死的相关性。目的研究ApoE基因启动子区DNA甲基化与动脉粥样硬化性脑梗死的相关性。方法随机抽取河南汉族人群52例,进行病例对照研究,动脉粥样硬化性脑梗死患者及健康对照者各26名,检测他们的ApoE基因启动子区DNA甲基化状态。结果1.病例组和对照组间高血压病史、颈动脉斑块的有无差异有统计学意义(P0.05),且病例组高于对照组。HCY、HDL-C、叶酸两组间比较(P0.05)差异有统计学意义;其中,病例组HDL-C、叶酸较对照组低,病例组HCY较对照组高。2.病例组和对照组间CpG14、CpG16的甲基化有显著差异(P0.05)。3.调整了性别和年龄及其他协变量后,病例组和对照组间CpG16、颈动脉粥样硬化斑块、叶酸有意义,OR值分别为16.146(95%CI:1.154~225.832),27.194(95%CI:2.266~326.362),0.586(95%CI:0.355~0.968),表明CpG16甲基化的人群发生动脉粥样硬化性脑梗死的风险是CpG16非甲基化人群的16.146倍,有颈动脉粥样硬化斑块的人群发生动脉粥样硬化性脑梗死的风险是无斑块人群的27.194倍。在一定范围内,叶酸含量越高,动脉粥样硬化性脑梗死发生风险越低。结论ApoE基因启动子区DNA甲基化、颈动脉粥样硬化斑块会增加动脉粥样硬化性脑梗死的发病风险,叶酸是动脉粥样硬化性脑梗死的保护因素。
[Abstract]:Background human apolipoprotein E (ApoE) gene is a key gene for liver clearance of residual lipoprotein, an important gene for anti atherosclerosis. The apolipoprotein E (ApoE) gene and its protein (ApoE) play a key role in lipid metabolism, including the redistribution of lipoprotein and cholesterol,.Apo E is divided into three common subtypes: E2, E3 and E4, fractions. Do not be encoded by the allele of epsilon 2, epsilon 3 and epsilon 4. A large number of people found that the epsilon 4 alleles can significantly increase the total cholesterol level of healthy people and make the carriers susceptible to atherosclerosis; on the contrary, the epsilon 2 allele can reduce the level of cholesterol in the carriers, and the effect of reducing the cholesterol is 2~ of the cholesterol effect of epsilon 4. 3 times. In addition, the epsilon 2, epsilon 3 and epsilon 4 alleles of the ApoE gene are also related to familial and sporadic Alzheimer's disease (AD). With the aging of the society, the incidence of cerebral infarction is increasing year by year. Among them, atherosclerotic cerebral infarction is the most common, accounting for 60% of all cerebral infarction. It is a focus of this study. Epigenetics is the result of genetic and environmental interaction. Epigenetics provides a new way of thinking for its research. Epigenetics is the change of gene sequence and gene expression, mainly including DNA methylation, histone modification, chromatin remodeling, non coded RNA regulation, and so on, which is based on DNA methylation. The aim of this experiment is to explore the correlation between DNA methylation of the promoter region of ApoE gene and atherosclerotic cerebral infarction. Objective to study the correlation between DNA methylation and atherosclerotic cerebral infarction in the promoter region of the ApoE gene. Methods 52 cases of Henan Han population were randomly selected, and the atherosclerotic cerebral infarction was studied and the atherosclerotic cerebral infarction was studied. 26 patients and 26 healthy controls were used to detect the DNA methylation status in the promoter region of their ApoE gene. Results there was a statistically significant difference in the history of hypertension between the 1. case group and the control group, and the difference in the carotid artery plaque was statistically significant (P0.05), and the case group was higher than the control group.HCY, HDL-C, and the comparison of the two groups of folic acid (P0.05) was statistically significant; among them, cases were statistically significant. Group HDL-C, folic acid was lower than that of the control group. The case group HCY was higher than the control group and CpG14 in the.2. case group and the control group. The methylation of CpG16 was significantly different (P0.05).3. adjusted the sex and age and the other co variables. The case group and the control group were CpG16, carotid atherosclerotic plaques, folic acid were significant, OR values were 16.146 (95%CI:1.154~225.832), 27.1 94 (95%CI:2.266~326.362), 0.586 (95%CI:0.355~0.968), indicating that the risk of atherosclerotic cerebral infarction in people with CpG16 methylation is 16.146 times as high as that of the non methylation population of CpG16, and the risk of atherosclerotic cerebral infarction in people with carotid atherosclerotic plaques is 27.194 times as high as that of the non plaque population. Within a certain range, leaves The higher the acid content, the lower the risk of atherosclerotic cerebral infarction. Conclusion DNA methylation in the promoter region of ApoE gene, carotid atherosclerotic plaque will increase the risk of atherosclerotic cerebral infarction, folic acid is a protective factor for atherosclerotic cerebral infarction.
【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R743.3
本文编号：2158931
[Abstract]:Background human apolipoprotein E (ApoE) gene is a key gene for liver clearance of residual lipoprotein, an important gene for anti atherosclerosis. The apolipoprotein E (ApoE) gene and its protein (ApoE) play a key role in lipid metabolism, including the redistribution of lipoprotein and cholesterol,.Apo E is divided into three common subtypes: E2, E3 and E4, fractions. Do not be encoded by the allele of epsilon 2, epsilon 3 and epsilon 4. A large number of people found that the epsilon 4 alleles can significantly increase the total cholesterol level of healthy people and make the carriers susceptible to atherosclerosis; on the contrary, the epsilon 2 allele can reduce the level of cholesterol in the carriers, and the effect of reducing the cholesterol is 2~ of the cholesterol effect of epsilon 4. 3 times. In addition, the epsilon 2, epsilon 3 and epsilon 4 alleles of the ApoE gene are also related to familial and sporadic Alzheimer's disease (AD). With the aging of the society, the incidence of cerebral infarction is increasing year by year. Among them, atherosclerotic cerebral infarction is the most common, accounting for 60% of all cerebral infarction. It is a focus of this study. Epigenetics is the result of genetic and environmental interaction. Epigenetics provides a new way of thinking for its research. Epigenetics is the change of gene sequence and gene expression, mainly including DNA methylation, histone modification, chromatin remodeling, non coded RNA regulation, and so on, which is based on DNA methylation. The aim of this experiment is to explore the correlation between DNA methylation of the promoter region of ApoE gene and atherosclerotic cerebral infarction. Objective to study the correlation between DNA methylation and atherosclerotic cerebral infarction in the promoter region of the ApoE gene. Methods 52 cases of Henan Han population were randomly selected, and the atherosclerotic cerebral infarction was studied and the atherosclerotic cerebral infarction was studied. 26 patients and 26 healthy controls were used to detect the DNA methylation status in the promoter region of their ApoE gene. Results there was a statistically significant difference in the history of hypertension between the 1. case group and the control group, and the difference in the carotid artery plaque was statistically significant (P0.05), and the case group was higher than the control group.HCY, HDL-C, and the comparison of the two groups of folic acid (P0.05) was statistically significant; among them, cases were statistically significant. Group HDL-C, folic acid was lower than that of the control group. The case group HCY was higher than the control group and CpG14 in the.2. case group and the control group. The methylation of CpG16 was significantly different (P0.05).3. adjusted the sex and age and the other co variables. The case group and the control group were CpG16, carotid atherosclerotic plaques, folic acid were significant, OR values were 16.146 (95%CI:1.154~225.832), 27.1 94 (95%CI:2.266~326.362), 0.586 (95%CI:0.355~0.968), indicating that the risk of atherosclerotic cerebral infarction in people with CpG16 methylation is 16.146 times as high as that of the non methylation population of CpG16, and the risk of atherosclerotic cerebral infarction in people with carotid atherosclerotic plaques is 27.194 times as high as that of the non plaque population. Within a certain range, leaves The higher the acid content, the lower the risk of atherosclerotic cerebral infarction. Conclusion DNA methylation in the promoter region of ApoE gene, carotid atherosclerotic plaque will increase the risk of atherosclerotic cerebral infarction, folic acid is a protective factor for atherosclerotic cerebral infarction.
【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R743.3
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