云南省突發(fā)性耳聾SOD2基因遺傳相關性研究
發(fā)布時間：2018-11-21 12:18
【摘要】：研究表明,突發(fā)性耳聾存在易感性差異,這種易感性差異可能與突發(fā)性耳聾的發(fā)病機制中有著重要生物學功能的基因有關。超氧化物歧化酶2(SOD2)是線粒體內(nèi)唯一的抗氧化酶,可保護、對抗內(nèi)耳免受自由基的損傷,其基因發(fā)生突變有可能影響超氧化物歧化酶2對內(nèi)耳的保護作用,從而增加個體突發(fā)性耳聾的患病風險。本項目著眼于超氧化物歧化酶2基因的突變與突發(fā)性耳聾病因?qū)W的關系,主要運用基因組DNA的提取、多重SnaPshot等技術研究超氧化物歧化酶2(SOD2)基因的多個單核苷酸多態(tài)性(SNP)位點與突發(fā)性耳聾的關系,并可基于此制備基因組探針,從而發(fā)現(xiàn)具有潛在突聾危險性的病患,在臨床上為分子診斷和個性化治療提供理論依據(jù)。 確定突發(fā)性耳聾的診斷標準診斷依據(jù)：1突然發(fā)生的,可在數(shù)分鐘、數(shù)小時或三天以內(nèi)。2非波動性感音神經(jīng)性聽力損失,可為輕、中或重度,甚至全聾。至少在相連的兩個頻率聽力下降20db以上。多為單側(cè),或偶有雙側(cè)同時或先后發(fā)生。3病因不明(未發(fā)現(xiàn)明確原因或者包括全身或局部因素)。4伴耳鳴、耳堵塞感。5伴眩暈、惡心、嘔吐,但不反復發(fā)作。6除了第八顱神經(jīng)外,無其他顱神經(jīng)受損癥狀。 突發(fā)性耳聾血樣采集程序和文件建立：由云南省第一人民醫(yī)院入院病人提供的診斷標準,保證病例收集符合國內(nèi)外流行病學調(diào)查規(guī)范并按同樣標準執(zhí)行。病史采集內(nèi)容：采用云南省第一人民醫(yī)院采血單,內(nèi)容含入院病人的基本信息、耳科病史、糖尿病等其他疾病。由醫(yī)生填寫并保存。 本課題共收集樣本165例,其中80例突發(fā)性耳聾患者,85例正�？刂平M。并采集外周靜脈血,通過采集肘靜脈血2ml, EDTA抗凝保存于-80度冰箱保存,提取全基因組DNA、并通過SnaPshot方法對SOD2基因位點進行SNP分型。 研究結果：在本次研究中,選取中國云南地區(qū)人群,一共165例中病人80,控制組85例,選取5個SNP位點(分別是rs5746136, rs5746129, rs2842960, rs4987023,rs4880),通過SnapShot基因分型,并用SPSS20.0進行卡方檢驗,發(fā)現(xiàn)突發(fā)性耳聾與SOD2基因的rs5746136位點存在易感性關系,其中AG基因型會賦予了突發(fā)性耳聾的風險(P=0.016; OR=2.136,95%CI=1.147-3.978)。其他位點并沒有發(fā)現(xiàn)和突發(fā)性耳聾具有相關性�？紤]到單倍型可能影響疾病的表型,于是我們在兩個組間進行單倍型頻率分析。由5個SNP位點進行構建單倍型,發(fā)現(xiàn)構建的單倍型在兩組間無統(tǒng)計學差異。
[Abstract]:The study shows that there is a difference in susceptibility to sudden deafness, which may be related to genes with important biological function in the pathogenesis of sudden deafness. Superoxide dismutase 2 (SOD2) is the only antioxidant enzyme in mitochondria, which can protect the inner ear from the damage of free radicals. The mutation of its gene may affect the protective effect of superoxide dismutase 2 on the inner ear. This increases the risk of sudden deafness in individuals. This project focuses on the relationship between the mutation of superoxide dismutase 2 gene and the etiology of sudden deafness, and mainly uses the extraction of genomic DNA. Multiple SnaPshot techniques were used to study the relationship between multiple single nucleotide polymorphism (SNP) loci of superoxide dismutase 2 (SOD2) gene and sudden deafness. It provides theoretical basis for molecular diagnosis and individualized therapy in clinic. The diagnostic criteria for sudden deafness were determined as follows: (1) sudden onset may occur within a few minutes, hours or three days. 2 Non-fluctuating sensorineural hearing loss may be mild, moderate or severe, or even total deafness. At least at two consecutive frequencies hearing loss 20db above. Most of them were unilateral, or occasionally occurred at the same time or successively on both sides. 3 unknown etiology (no definite cause or including systemic or local factors). 4 tinnitus, ear clogging feeling. 5 with vertigo, nausea, vomiting. But no recurrent attacks. 6 except the eighth cranial nerve, no other cranial nerve damage symptoms. Establishment of procedures and documents for collecting blood samples of sudden deafness: diagnostic criteria provided by patients admitted to the first people's Hospital of Yunnan Province ensure that the collection of cases conforms to the epidemiological investigation norms at home and abroad and is carried out in accordance with the same standards. Collection of medical history: the first people's Hospital of Yunnan Province was used to collect blood, which contained the basic information of the hospitalized patients, the history of otology, diabetes and other diseases. Fill in and save by the doctor. A total of 165 samples were collected, including 80 sudden deafness patients and 85 normal control groups. The peripheral venous blood was collected, and the EDTA anticoagulant was stored in -80 degree refrigerator. The whole genome DNA, was extracted and the SNP typing of SOD2 locus was carried out by SnaPshot method. Results: in this study, 80 out of 165 patients were selected from Yunnan region of China, 85 from control group, 5 SNP loci (rs5746136, rs5746129, rs2842960, rs4987023,rs4880) were selected, and SnapShot genotyping was used. By using SPSS20.0 chi-square test, we found that sudden deafness was susceptible to rs5746136 locus of SOD2 gene, and the AG genotype was associated with the risk of sudden deafness (P0. 016). OR=2.136,95%CI=1.147-3.978) No other loci were found to be associated with sudden deafness. Considering that haplotypes may affect disease phenotypes, we performed haplotype frequency analysis between the two groups. Haplotypes were constructed from 5 SNP loci, and there was no statistical difference between the two groups.
【學位授予單位】：昆明理工大學
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R764
本文編號：2346945
[Abstract]:The study shows that there is a difference in susceptibility to sudden deafness, which may be related to genes with important biological function in the pathogenesis of sudden deafness. Superoxide dismutase 2 (SOD2) is the only antioxidant enzyme in mitochondria, which can protect the inner ear from the damage of free radicals. The mutation of its gene may affect the protective effect of superoxide dismutase 2 on the inner ear. This increases the risk of sudden deafness in individuals. This project focuses on the relationship between the mutation of superoxide dismutase 2 gene and the etiology of sudden deafness, and mainly uses the extraction of genomic DNA. Multiple SnaPshot techniques were used to study the relationship between multiple single nucleotide polymorphism (SNP) loci of superoxide dismutase 2 (SOD2) gene and sudden deafness. It provides theoretical basis for molecular diagnosis and individualized therapy in clinic. The diagnostic criteria for sudden deafness were determined as follows: (1) sudden onset may occur within a few minutes, hours or three days. 2 Non-fluctuating sensorineural hearing loss may be mild, moderate or severe, or even total deafness. At least at two consecutive frequencies hearing loss 20db above. Most of them were unilateral, or occasionally occurred at the same time or successively on both sides. 3 unknown etiology (no definite cause or including systemic or local factors). 4 tinnitus, ear clogging feeling. 5 with vertigo, nausea, vomiting. But no recurrent attacks. 6 except the eighth cranial nerve, no other cranial nerve damage symptoms. Establishment of procedures and documents for collecting blood samples of sudden deafness: diagnostic criteria provided by patients admitted to the first people's Hospital of Yunnan Province ensure that the collection of cases conforms to the epidemiological investigation norms at home and abroad and is carried out in accordance with the same standards. Collection of medical history: the first people's Hospital of Yunnan Province was used to collect blood, which contained the basic information of the hospitalized patients, the history of otology, diabetes and other diseases. Fill in and save by the doctor. A total of 165 samples were collected, including 80 sudden deafness patients and 85 normal control groups. The peripheral venous blood was collected, and the EDTA anticoagulant was stored in -80 degree refrigerator. The whole genome DNA, was extracted and the SNP typing of SOD2 locus was carried out by SnaPshot method. Results: in this study, 80 out of 165 patients were selected from Yunnan region of China, 85 from control group, 5 SNP loci (rs5746136, rs5746129, rs2842960, rs4987023,rs4880) were selected, and SnapShot genotyping was used. By using SPSS20.0 chi-square test, we found that sudden deafness was susceptible to rs5746136 locus of SOD2 gene, and the AG genotype was associated with the risk of sudden deafness (P0. 016). OR=2.136,95%CI=1.147-3.978) No other loci were found to be associated with sudden deafness. Considering that haplotypes may affect disease phenotypes, we performed haplotype frequency analysis between the two groups. Haplotypes were constructed from 5 SNP loci, and there was no statistical difference between the two groups.
【學位授予單位】：昆明理工大學
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R764
【參考文獻】
相關期刊論文 前10條
1 汪運坤;王麗雯;王博惕;;高脂蛋白血癥對內(nèi)耳的損害[J];國外醫(yī)學.耳鼻咽喉科學分冊;1993年06期
2 史曉瑞;內(nèi)皮舒張因子——內(nèi)源性硝基血管擴張劑與內(nèi)耳微循環(huán)[J];國外醫(yī)學.耳鼻咽喉科學分冊;1996年06期
3 羅志強;耳蝸微循環(huán)的自身調(diào)節(jié)機制[J];國外醫(yī)學.耳鼻咽喉科學分冊;2001年04期
4 丁娟;幾種神經(jīng)肽在內(nèi)耳中的分布和作用[J];國外醫(yī)學.耳鼻咽喉科學分冊;2001年04期
5 王穎,褚迅,黃薇;單核苷酸多態(tài)性研究及其對人類醫(yī)學的影響[J];基礎醫(yī)學與臨床;2004年06期
6 陸明雄,呂元彬;突聾、美尼爾氏病和貝爾氏面癱患者血粘度變化的初步分析[J];臨床耳鼻咽喉科雜志;1987年04期
7 田豐,盧永德,陳忠;突發(fā)性耳聾患者前列環(huán)素I_2和血栓素A_2的含量變化[J];臨床耳鼻咽喉科雜志;1993年04期
8 楊杪,譚皓,鄭建如,王峰,蔣長征,何美安,陳永文,鄔堂春;質(zhì)膜Ca~(2+)-ATP酶異構體2基因多態(tài)性與噪聲性聽力損失易感性的關系[J];中國工業(yè)醫(yī)學雜志;2005年01期
9 蔣春榮,殷團芳,盧永德,徐敏;突聾與微循環(huán)障礙的關系[J];中國耳鼻咽喉顱底外科雜志;1999年01期
10 李旭東;陳建雄;耿繼武;閆雪華;溫翠菊;楊敏;黎麗春;鄒劍明;;SOD2單倍型與噪聲性聽力損失易感性的關聯(lián)研究[J];中國衛(wèi)生工程學;2010年04期
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