【摘要】：背景人類的載脂蛋白E(ApoE)基因是肝清除殘余脂蛋白的一個(gè)關(guān)鍵基因,一種抗動(dòng)脈粥樣硬化的重要基因。載脂蛋白E(ApoE)基因及其蛋白(ApoE)在脂質(zhì)代謝中發(fā)揮關(guān)鍵作用,包括脂蛋白和膽固醇的再分配。Apo E分為三個(gè)常見的亞型:E2、E3和E4,分別被ε2、ε3和ε4三個(gè)等位基因編碼。大量人群調(diào)查發(fā)現(xiàn)ε4等位基因可以顯著地升高健康人的總膽固醇水平,使攜帶者易患動(dòng)脈粥樣硬化;相反,ε2等位基因可以降低攜帶者的膽固醇水平,而且其降低膽固醇的效應(yīng)是ε4升高膽固醇效應(yīng)的2~3倍。此外,ApoE基因的ε2、ε3和ε4等位基因也與家族性和散發(fā)性阿爾茨海默病(AD)有關(guān)。隨著社會(huì)的老齡化,腦梗死的發(fā)病率逐年上升,其中,動(dòng)脈粥樣硬化性腦梗死最為常見,約占全部腦梗死的60%,是本研究的關(guān)注點(diǎn)。腦梗死是一種多基因遺傳疾病,是遺傳和環(huán)境相互作用的結(jié)果,表觀遺傳學(xué)為其研究提供了新思路。表觀遺傳學(xué)是基因序列不變,基因表達(dá)發(fā)生可遺傳的改變,主要包括DNA甲基化、組蛋白修飾、染色質(zhì)重塑、非編碼RNA調(diào)控等,目前研究較為深入的是DNA甲基化�；谝陨�,本實(shí)驗(yàn)旨在探索ApoE基因啟動(dòng)子區(qū)DNA甲基化與動(dòng)脈粥樣硬化性腦梗死的相關(guān)性。目的研究ApoE基因啟動(dòng)子區(qū)DNA甲基化與動(dòng)脈粥樣硬化性腦梗死的相關(guān)性。方法隨機(jī)抽取河南漢族人群52例,進(jìn)行病例對(duì)照研究,動(dòng)脈粥樣硬化性腦梗死患者及健康對(duì)照者各26名,檢測他們的ApoE基因啟動(dòng)子區(qū)DNA甲基化狀態(tài)。結(jié)果1.病例組和對(duì)照組間高血壓病史、頸動(dòng)脈斑塊的有無差異有統(tǒng)計(jì)學(xué)意義(P0.05),且病例組高于對(duì)照組。HCY、HDL-C、葉酸兩組間比較(P0.05)差異有統(tǒng)計(jì)學(xué)意義;其中,病例組HDL-C、葉酸較對(duì)照組低,病例組HCY較對(duì)照組高。2.病例組和對(duì)照組間CpG14、CpG16的甲基化有顯著差異(P0.05)。3.調(diào)整了性別和年齡及其他協(xié)變量后,病例組和對(duì)照組間CpG16、頸動(dòng)脈粥樣硬化斑塊、葉酸有意義,OR值分別為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甲基化的人群發(fā)生動(dòng)脈粥樣硬化性腦梗死的風(fēng)險(xiǎn)是CpG16非甲基化人群的16.146倍,有頸動(dòng)脈粥樣硬化斑塊的人群發(fā)生動(dòng)脈粥樣硬化性腦梗死的風(fēng)險(xiǎn)是無斑塊人群的27.194倍。在一定范圍內(nèi),葉酸含量越高,動(dòng)脈粥樣硬化性腦梗死發(fā)生風(fēng)險(xiǎn)越低。結(jié)論ApoE基因啟動(dòng)子區(qū)DNA甲基化、頸動(dòng)脈粥樣硬化斑塊會(huì)增加動(dòng)脈粥樣硬化性腦梗死的發(fā)病風(fēng)險(xiǎn),葉酸是動(dòng)脈粥樣硬化性腦梗死的保護(hù)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.
【學(xué)位授予單位】：鄭州大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R743.3

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