云南省突發(fā)性耳聾SOD2基因遺傳相關(guān)性研究
發(fā)布時(shí)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(jī)制中有著重要生物學(xué)功能的基因有關(guān)。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(hù)、對(duì)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(duì)內(nèi)耳的保護(hù)作用,從而增加個(gè)體突發(fā)性耳聾的患病風(fēng)險(xiǎn)。本項(xiàng)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(guān)系,主要運(yùn)用基因組DNA的提取、多重SnaPshot等技術(shù)研究超氧化物歧化酶2(SOD2)基因的多個(gè)單核苷酸多態(tài)性(SNP)位點(diǎn)與突發(fā)性耳聾的關(guān)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(xiǎn)性的病患,在臨床上為分子診斷和個(gè)性化治療提供理論依據(jù)。 確定突發(fā)性耳聾的診斷標(biāo)準(zhǔn)診斷依據(jù)：1突然發(fā)生的,可在數(shù)分鐘、數(shù)小時(shí)或三天以內(nèi)。2非波動(dòng)性感音神經(jīng)性聽(tīng)力損失,可為輕、中或重度,甚至全聾。至少在相連的兩個(gè)頻率聽(tīng)力下降20db以上。多為單側(cè),或偶有雙側(cè)同時(shí)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(fù)發(fā)作。6除了第八顱神經(jīng)外,無(wú)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(biāo)準(zhǔn),保證病例收集符合國(guó)內(nèi)外流行病學(xué)調(diào)查規(guī)范并按同樣標(biāo)準(zhǔn)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(xiě)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(guò)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(guò)SnaPshot方法對(duì)SOD2基因位點(diǎn)進(jìn)行SNP分型。 研究結(jié)果：在本次研究中,選取中國(guó)云南地區(qū)人群,一共165例中病人80,控制組85例,選取5個(gè)SNP位點(diǎn)(分別是rs5746136, rs5746129, rs2842960, rs4987023,rs4880),通過(guò)SnapShot基因分型,并用SPSS20.0進(jìn)行卡方檢驗(yàn),發(fā)現(xiàn)突發(fā)性耳聾與SOD2基因的rs5746136位點(diǎn)存在易感性關(guān)系,其中AG基因型會(huì)賦予了突發(fā)性耳聾的風(fēng)險(xiǎn)(P=0.016; OR=2.136,95%CI=1.147-3.978)。其他位點(diǎn)并沒(méi)有發(fā)現(xiàn)和突發(fā)性耳聾具有相關(guān)性�？紤]到單倍型可能影響疾病的表型,于是我們?cè)趦蓚�(gè)組間進(jìn)行單倍型頻率分析。由5個(gè)SNP位點(diǎn)進(jìn)行構(gòu)建單倍型,發(fā)現(xiàn)構(gòu)建的單倍型在兩組間無(wú)統(tǒng)計(jì)學(xué)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(xué)位授予單位】：昆明理工大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R764
本文編號(hào)：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(xué)位授予單位】：昆明理工大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R764
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