本文選題：miR-126 + 基因�。� 參考：《右江民族醫(yī)學(xué)院》2017年碩士論文

【摘要】：目的:檢測廣西地區(qū)健康人群miR-126基因rs4636297G/A多態(tài)性位點的分布頻率,并與其他不同地區(qū)人群rs4636297G/A位點的分布頻率進(jìn)行比較,揭示廣西地區(qū)健康人群rs4636297G/A位點的分布特點。方法:采用單堿基延伸的聚合酶鏈?zhǔn)椒磻?yīng)(Snapshot PCR)基因分型技術(shù)和DNA測序的方法來檢測廣西地區(qū)456例健康人miR-126基因rs4636297G/A的多態(tài)性,統(tǒng)計rs4636297G/A位點的基因型和等位基因的頻率分布;通過Pub Med(SNP)數(shù)據(jù)庫獲取人類基因組計劃公布的中國北京人群、歐洲人群、日本人群及非洲人群的rs4636297G/A位點分型數(shù)據(jù);將廣西地區(qū)人群rs4636297G/A多態(tài)性位點分型數(shù)據(jù)與其他四個地區(qū)人群的分型數(shù)據(jù)進(jìn)行比較,來分析這五個地區(qū)人群的多態(tài)性位點頻率分布的異同。結(jié)果:根據(jù)基因分型技術(shù)和DNA測序的方法檢測的結(jié)果可知,廣西地區(qū)健康人群miR-126基因rs4636297G/A位點存在多態(tài)性,并具有三種基因型,且多態(tài)性性分布均符合Hardy-Weinberg遺傳平衡定律(P0.05),具有明顯的群體代表性。將廣西地區(qū)miR-126基因rs4636297G/A位點的分型數(shù)據(jù)與其他四個地區(qū)的分型數(shù)據(jù)比較發(fā)現(xiàn),miR-126基因rs4636297G/A位點在廣西人群、北京和日本人群間多態(tài)性的分布無顯著性差異(P均0.05),而miR-126基因rs4636297G/A位點在廣西人群和其他兩個人群間的頻率分布存在顯著性的差異(P均0.05)。結(jié)論:在廣西地區(qū)健康人群中存在miR-126基因rs4636297G/A位點多態(tài)性,且多態(tài)性分布均符合Hardy-Weinberg遺傳平衡定律(P0.05),說明具有明顯的群體代表性。MiR-126基因rs4636297G/A位點多態(tài)性的分布在廣西地區(qū)和其他地區(qū)人群不完全一致,這可能是不同地區(qū)人群對疾病的易感性表現(xiàn)出差異的原因之一。目的:探討miR-126基因rs4636297G/A多態(tài)性與缺血性腦卒中發(fā)生的遺傳易感性,檢測缺血性腦卒中患者與正常人群中miR-126的表達(dá)水平,并分析miR-126基因rs4636297G/A多態(tài)性與miR-126的表達(dá)是否存在相關(guān)性。方法:采用單堿基延伸的聚合酶鏈?zhǔn)椒磻?yīng)(Snapshot PCR)基因分型技術(shù)和DNA測序的方法來檢測廣西地區(qū)456例健康人和592例缺血性腦卒中患者miR-126基因rs4636297G/A多態(tài)性位點的多態(tài)性,計算rs4636297G/A多態(tài)性位點在健康對照組及病例組中的基因型和等位基因的頻率分布,利用統(tǒng)計軟件分析miR-126基因rs4636297G/A多態(tài)性與缺血性腦卒中發(fā)生的遺傳易感性。利用SYBR Green實時熒光定量PCR的方法檢測病例對照組中miR-126的表達(dá)水平,并分析miR-126基因rs4636297G/A多態(tài)性與miR-126表達(dá)的相關(guān)性。結(jié)果:MiR-126基因rs4636297G/A位點在病例和對照組中都存在多態(tài)性,分別具有三種基因型,且rs4636297G/A多態(tài)性位點在病例對照組中的頻率分布均符合Hardy-Weinberg遺傳平衡定律(P均0.05),具有明顯的群體代表性。在本次研究中我們發(fā)現(xiàn)miR-126基因rs4636297G/A位點的頻率分布在缺血性腦卒中病人及健康人群間存在顯著性差異(P0.05)。與健康人群相比較,缺血性腦卒中患者GA(33.8%vs.24.8%)和AA(5.9%vs.2.5%)基因型的頻率顯著降低,GA和AA基因型與缺血性腦卒中的發(fā)生負(fù)相關(guān)(GA vs.GG:OR=0.61,95%CI=0.47-0.80,P0.001;AA vs.GG:OR=0.36,95%CI=0.19-0.68,P=0.001);進(jìn)行遺傳模型分析后發(fā)現(xiàn)miR-126基因rs4636297G/A位點的顯性模型和隱性模型在病例對照組間均存在顯著差異(顯性模型,AA+GA vs.GG:OR=0.57,95%CI=0.44-0.74,P0.001;隱性模型,AA vs.GA+AA:OR=0.41,95%CI=0.22-0.79,P=0.006)。通過納入缺血性腦卒中的常見風(fēng)險因素,年齡、性別、吸煙、高血壓、糖尿病、甘油三酯、膽固醇、低密度脂蛋白及高密度脂蛋白進(jìn)行l(wèi)ogistic回歸校正計算后發(fā)現(xiàn),miR-126基因rs4636297G/A多態(tài)性位點的基因型及遺傳模型的分布在病例對照間仍然存在顯著性的差異(GA vs.GG:AOR=0.64,95%CI=0.44-0.95,P=0.025;AA vs.GG:AOR=0.32,95%CI=0.14-0.74,P=0.007;顯性模型,AA+GA vs.GG:AOR=0.58,95%CI=0.40-0.84,P=0.004;隱性模型,AA vs.GA+AA:AOR=0.37,95%CI=0.16-0.82,P=0.015)。與正常組對比,缺血性腦卒中病人中miR-126的表達(dá)顯著降低(缺血性腦卒中組vs.對照組=6.57±1.50 vs.9.86±1.92,P0.001),攜帶GA/AA基因型的患者其miR-126表達(dá)水平顯著高于攜帶GG患者的miR-126表達(dá)水平(GG vs.GA/AA=6.08±1.47 vs.7.53±2.00,P0.001);正常對照組中rs4636297G/A多態(tài)性與miR-126的表達(dá)不存在相關(guān)性(GG vs.GA/AA=9.77±1.67 vs.10.6±1.19,P=0.485)。結(jié)論:MiR-126基因rs4636297G/A位點GA/AA基因型頻率在缺血性腦卒中患者中顯著減少,與缺血性腦卒中的發(fā)生存在負(fù)相關(guān)性,miR-126基因rs4636297G/A位點可能是缺血性腦卒中發(fā)生的一個保護(hù)性的因素。此外,缺血性腦卒中患者中異常減少miR-126可能是其潛在的生物學(xué)標(biāo)記或者治療靶標(biāo)。目的:檢測廣西地區(qū)健康人群miR-21基因rs1292037T/C多態(tài)性位點的分布頻率,并與不同地區(qū)人群進(jìn)行比較,揭示廣西地區(qū)rs1292037T/C多態(tài)性位點的分布特點,為后續(xù)的關(guān)聯(lián)性研究奠定遺傳學(xué)基礎(chǔ)。方法:采用單堿基延伸的聚合酶鏈?zhǔn)椒磻?yīng)(Snapshot PCR)基因分型技術(shù)和DNA測序的方法來檢測廣西地區(qū)456例健康人群rs1292037T/C多態(tài)性位點的多態(tài)性,統(tǒng)計這個位點的基因型和等位基因的頻率分布;通過Pub Med(SNP)數(shù)據(jù)庫來獲取人類基因組計劃公布的中國北京人群、歐洲人群、日本人群及非洲人群的SNPs分型數(shù)據(jù);將廣西地區(qū)人群的rs1292037T/C多態(tài)性位點分型數(shù)據(jù)與其他四個地區(qū)人群的分型數(shù)據(jù)進(jìn)行比較,來分析這五個地區(qū)人群的多態(tài)性位點頻率分布的異同。結(jié)果:根據(jù)基因分型技術(shù)和DNA測序的方法檢測的結(jié)果可知,廣西地區(qū)人群miR-21基因rs1292037T/C位點存在多態(tài)性,并且具有三種基因型,rs1292037T/C的多態(tài)性分布符合Hardy-Weinberg遺傳平衡定律(P0.05),具有明顯的群體代表性。將廣西地區(qū)miR-21基因rs1292037T/C位點的分型數(shù)據(jù)與其他四個地區(qū)的分型數(shù)據(jù)比較發(fā)現(xiàn),miR-21rs1292037T/C位點在廣西人群和北京人群間的頻率分布無顯著性差異(P0.05),而rs1292037T/C位點在廣西人群和其他地區(qū)三個人群間的頻率分布存在顯著性的差異(P均0.05)。結(jié)論:在廣西地區(qū)人群中存在miR-21基因rs1292037T/C多態(tài)性,rs1292037T/C多態(tài)性分布符合Hardy-Weinberg遺傳平衡定(P0.05),具有明顯的群體代表性。miR-21基因rs1292037T/C多態(tài)性的分布在廣西地區(qū)和其他地區(qū)人群不一致,這可能是不同地區(qū)人群對疾病易感性表現(xiàn)出差異的原因之一。目的:探討miR-21基因rs1292037T/C多態(tài)性與缺血性腦卒中發(fā)生的遺傳易感性,檢測缺血性腦卒中患者與正常人群中miR-21的表達(dá)水平,并分析miR-21基因rs1292037T/C多態(tài)性與miR-21的表達(dá)是否存在相關(guān)性。方法:采用單堿基延伸的聚合酶鏈?zhǔn)椒磻?yīng)(Snapshot PCR)基因分型技術(shù)和DNA測序的方法來檢測廣西地區(qū)456健康對照人群和592例缺血性腦卒中患者miR-21基因rs1292037T/C位點的多態(tài)性,計算rs1292037T/C多態(tài)性位點在健康對照組及病例組中的基因型和等位基因的頻率分布,通過統(tǒng)計軟件來評估m(xù)iR-21基因rs1292037T/C多態(tài)性與缺血性腦卒中發(fā)生的遺傳易感性。利用SYBR Green實時熒光定量PCR的方法檢測病例對照組中miR-21的表達(dá)水平,并分析miR-21基因rs1292037T/C多態(tài)性與miR-21表達(dá)的相關(guān)性。結(jié)果:MiR-21基因rs1292037T/C位點在病例和對照組中都存在多態(tài)性,rs1292037T/C位點具有三種基因型,rs1292037T/C多態(tài)性位點在病例對照組中的頻率分布均符合Hardy-Weinberg遺傳平衡定律(P均0.05),具有明顯的群體代表性。在本次研究中我們發(fā)現(xiàn)rs1292037T/C多態(tài)性位點的頻率分布在缺血性腦卒中病人及健康人群間不存在顯著性差異(P0.05)。進(jìn)行遺傳模型分析后發(fā)現(xiàn)miR-21基因rs1292037T/C位點顯性模型和隱性模型在病例對照組間也不存在顯著差異(顯性模型,CC+CT vs.TT:OR=1.22,95%CI=0.94-1.59,P=0.137;隱性模型,CC vs.CT+TT:OR=1.24,95%CI=0.90-1.71,P=0.191)。通過納入缺血性腦卒中的常見風(fēng)險因素如年齡、性別、吸煙、高血壓、糖尿病、甘油三酯、膽固醇、低密度脂蛋白及高密度脂蛋白進(jìn)行l(wèi)ogistic回歸校正計算后發(fā)現(xiàn),rs1292037T/C多態(tài)性位點的基因型及遺傳模型的分布在病例對照間的分布仍然不存在顯著性的差異(CT vs.TT:AOR=1.21,95%CI=0.81-1.80,P=0.349;CC vs.TT:AOR=1.47,95%CI=0.86-2.50,P=0.159;顯性模型,CC+CT vs.TT:OR=1.28,95%CI=0.88-1.86,P=0.204;隱性模型,CC vs.CT+TT:OR=1.37,95%CI=0.85-2.21,P=0.192),提示rs1292037T/C多態(tài)性可能與缺血性腦卒中的發(fā)生無相關(guān)性。在缺血性腦卒中病人中miR-21的表達(dá)顯著升高(缺血性腦卒中組vs.對照組=34.65±7.26 vs.26.89±6.81,P0.001),但miR-21的表達(dá)水平與rs1292037T/C多態(tài)性無關(guān)。結(jié)論:MiR-21基因rs1292037T/C多態(tài)性與缺血性腦卒中的發(fā)生不存在相關(guān)性,缺血性腦卒中患者中異常增高的miR-21可能是其潛在的生物學(xué)標(biāo)記和治療靶標(biāo)。
[Abstract]:Objective: to detect the distribution frequency of miR-126 gene rs4636297G/A polymorphic loci in healthy people in Guangxi, and to compare the distribution frequency of rs4636297G/A loci with other people in other regions, to reveal the distribution of rs4636297G/A loci in healthy people in Guangxi. Method: single base extension polymerase chain reaction (Snapshot PCR). Genotyping and DNA sequencing methods were used to detect the polymorphism of miR-126 gene rs4636297G/A in 456 healthy people in Guangxi, and the frequency distribution of genotypes and alleles of the rs4636297G/A loci were statistically analyzed. The human genome project, the European population, the Japanese population and the Africans, were obtained by the Pub Med (SNP) database. The rs4636297G/A polymorphism data of the group were compared with the typing data of the rs4636297G/A polymorphic loci in the Guangxi population and the other four regions, to analyze the similarities and differences in the frequency distribution of polymorphic loci in the five regions. The miR-126 gene rs4636297G/A loci of the healthy people in the western region have polymorphism and have three genotypes, and the polymorphic distribution conforms to the Hardy-Weinberg's law of genetic balance (P0.05). It has a distinct population representation. The classification data of the rs4636297G/A loci of the miR-126 gene in Guangxi area are compared with the other four regions. It was found that there was no significant difference in the distribution of polymorphism between the miR-126 gene rs4636297G/A loci in Guangxi population, Beijing and the Japanese group (P 0.05), while the frequency distribution of miR-126 gene rs4636297G/A locus in Guangxi population and other two groups was significantly different (P 0.05). Conclusion: there is miR-126 in the healthy population of Guangxi. The polymorphism of the gene rs4636297G/A locus and the polymorphism distribution conform to the Hardy-Weinberg's law of genetic balance (P0.05), indicating that the distribution of the rs4636297G/A locus polymorphism of the group representative.MiR-126 gene is not exactly the same in the Guangxi region and other populations. This can be the expression of the susceptibility to disease in different regions. Objective: To investigate the genetic susceptibility of miR-126 gene rs4636297G/A polymorphism to ischemic stroke, to detect the expression level of miR-126 in ischemic stroke patients and normal people, and to analyze the correlation between the miR-126 gene rs4636297G/A polymorphism and the expression of miR-126. Method: single base extension is used. Polymerase chain reaction (Snapshot PCR) genotyping and DNA sequencing were used to detect the polymorphism of miR-126 gene polymorphism loci in 456 healthy and 592 ischemic stroke patients in Guangxi, and to calculate the genotype and allele frequency of rs4636297G/A polymorphic loci in the healthy control group and the case group. Rate distribution, the miR-126 gene rs4636297G/A polymorphism and the genetic susceptibility to ischemic stroke were analyzed by statistical software. The expression level of miR-126 in the case control group was detected by SYBR Green real-time fluorescent quantitative PCR, and the correlation between the miR-126 gene rs4636297G/A polymorphism and miR-126 expression was analyzed. The result: MiR-126 gene. Rs4636297G/A loci have polymorphism in both cases and control groups, with three genotypes, respectively, and the frequency distribution of rs4636297G/A polymorphic loci in case control group conforms to Hardy-Weinberg's law of genetic balance (P 0.05), which has obvious population representation. In this study, we found the rs4636297G/A locus of the miR-126 gene. There was a significant difference in frequency distribution between ischemic stroke patients and healthy people (P0.05). Compared with healthy people, the frequency of GA (33.8%vs.24.8%) and AA (5.9%vs.2.5%) genotypes in ischemic stroke patients decreased significantly, and GA and AA genotypes were negatively correlated with ischemic stroke (GA vs.GG:OR=0.61,95%CI=0.47-0.80, P0.001). AA vs.GG:OR=0.36,95%CI=0.19-0.68, P=0.001); after the analysis of the genetic model, the dominant and recessive models of the miR-126 gene rs4636297G/A locus were significantly different between the case control groups (dominant model, AA+GA vs.GG:OR=0.57,95%CI=0.44-0.74, P0.001; implicit model, AA vs.GA+AA:OR=0.41,95%CI=0.22-0.79, P=0.006). Logistic regression analysis of the common risk factors for ischemic stroke, age, sex, smoking, hypertension, diabetes, triglycerides, cholesterol, low density lipoprotein and HDL, found that the genotype and genetic model of the miR-126 gene rs4636297G/A polymorphism still remained in case control. In significant differences (GA vs.GG:AOR=0.64,95%CI=0.44-0.95, P=0.025; AA vs.GG:AOR=0.32,95%CI=0.14-0.74, P=0.007; dominant model, AA+GA vs.GG:AOR=0.58,95%CI=0.40-0.84, P=0.004; recessive model, AA vs.GA+AA:AOR=0.37,95%CI=0.16-0.82, P=0.015). In the ischemic stroke group, the vs. control group was =6.57 + 1.50 vs.9.86 + 1.92, P0.001). The level of miR-126 expression in the patients carrying GA/AA genotype was significantly higher than that of the GG patients (GG vs.GA/AA=6.08 + 1.47 vs.7.53 + 2, P0.001), and there was no correlation between the normal control group and the expression of the normal control group. A=9.77 + 1.67 vs.10.6 + 1.19, P=0.485). Conclusion: the frequency of GA/AA genotype of rs4636297G/A locus of MiR-126 gene is significantly reduced in ischemic stroke patients and has a negative correlation with the occurrence of ischemic stroke. The rs4636297G/A site of miR-126 gene may be a protective factor for ischemic stroke. In addition, ischemic brain Abnormal reduction of miR-126 in stroke patients may be a potential biological marker or therapeutic target. Objective: to detect the distribution frequency of rs1292037T/C polymorphic loci of the miR-21 gene in healthy people in Guangxi and to compare the distribution of the rs1292037T/C polymorphic loci in the Guangxi region. The genetic basis of sex study was established. Methods: single base extended polymerase chain reaction (Snapshot PCR) genotyping and DNA sequencing were used to detect polymorphism of rs1292037T/C polymorphic loci in 456 healthy people in Guangxi region, and the frequency distribution of genotypes and alleles of this site was statistically analyzed; the number of Pub Med (SNP) numbers was measured. The SNPs classification data of the Chinese Beijing population, the European population, the Japanese population and the African population were obtained from the human genome project, and the rs1292037T/C polymorphic loci data of the Guangxi population were compared with the subtypes of the other four regions to analyze the frequency of polymorphic loci in the five regions. Results: according to the results of genotyping and DNA sequencing, the rs1292037T/C loci of miR-21 gene in Guangxi population are polymorphic and have three genotypes. The polymorphism distribution of rs1292037T/C conforms to the Hardy-Weinberg's law of genetic balance (P0.05). It has a distinct population representation. It will be the place of Guangxi. Compared with the typing data of the other four regions, the rs1292037T/C loci of the region miR-21 gene showed that there was no significant difference in the frequency distribution of the miR-21rs1292037T/C loci between the Guangxi population and the Beijing population (P0.05), while the frequency distribution of the rs1292037T/C locus between the Guangxi population and the other three populations had a significant difference. Difference (P 0.05). Conclusion: there is a rs1292037T/C polymorphism of miR-21 gene in the population of Guangxi, and the distribution of rs1292037T/C polymorphism conforms to Hardy-Weinberg genetic balance (P0.05). The distribution of rs1292037T/C polymorphism of the group representative.MiR-21 gene is not consistent with those in other regions, which may be different regions. One of the reasons for the difference in susceptibility to disease. Objective: To investigate the genetic susceptibility of miR-21 gene rs1292037T/C polymorphism to ischemic stroke, to detect the expression level of miR-21 in ischemic stroke patients and normal population, and to analyze the correlation between the rs1292037T/ C polymorphism of miR-21 gene and the expression of miR-21. Methods: single base extended polymerase chain reaction (Snapshot PCR) genotyping and DNA sequencing were used to detect the polymorphism of miR-21 gene rs1292037T/C loci in 456 healthy controls and 592 patients with ischemic stroke in Guangxi area, and to calculate the genes of rs1292037T/C polymorphic loci in healthy control and case groups. The frequency distribution of the genotype and allele was used to evaluate the genetic susceptibility of the miR-21 gene rs1292037T/C polymorphism to the ischemic stroke. The expression of miR-21 in the case control group was detected by SYBR Green real-time fluorescent quantitative PCR, and the correlation between the miR-21 based rs1292037T/C polymorphism and the miR-21 expression was analyzed. Results: MiR-21 gene rs1292037T/C loci were polymorphic in both cases and control groups, and there were three genotypes in rs1292037T/C loci. The frequency distribution of rs1292037T/C polymorphic loci in case control group all conformed to Hardy-Weinberg's law of genetic balance (P 0.05). The frequency distribution of the present rs1292037T/C polymorphic loci was not significant difference between the ischemic stroke patients and the healthy people (P0.05). After the genetic model analysis, it was found that there was no significant difference between the dominant and recessive model of the miR-21 gene rs1292037T/C locus in the case control group (the dominant model, CC+CT vs.TT:OR=1.22,95%CI=0.). 94-1.59, P=0.137; recessive model, CC vs.CT+TT:OR=1.24,95%CI=0.90-1.71, P=0.191). The rs1292037T/C polymorphism was found by logistic regression analysis of common risk factors included in ischemic stroke such as age, sex, smoking, hypertension, diabetes, triglycerides, cholesterol, low density lipoprotein and high density lipoprotein. The distribution of point genotypes and genetic models still had no significant difference between the distribution of case control (CT vs.TT:AOR=1.21,95%CI=0.81-1.80, P=0.349; CC vs.TT:AOR=1.47,95%CI=0.86-2.50, P=0.159; dominant model, CC+CT vs.TT:OR=1.28,95%CI=0.88-1.86, P=0.204; recessive model, CC vs.CT+TT:OR=1.37,95%CI=0.85-2.21, P=0.192), It is suggested that rs1292037T/C polymorphism may not be associated with the occurrence of ischemic stroke. The expression of miR-21 in ischemic stroke patients is significantly elevated (=34.65 + 7.26 vs.26.89 + 6.81, P0.001) in ischemic stroke group (vs. control group), but the expression level of miR-21 is not related to rs1292037T/C polymorphisms. Conclusion: MiR-21 gene rs1292037T/C polymorphism There is no correlation between the occurrence of ischemic stroke and the occurrence of ischemic stroke. The abnormally high miR-21 in ischemic stroke may be its potential biological marker and therapeutic target.

【學(xué)位授予單位】：右江民族醫(yī)學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R743.3

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本文編號：1869830