本文選題：基因 + 耳聾��； 參考：《中國人民解放軍軍醫(yī)進修學(xué)院》2010年博士論文

【摘要】： 聽力障礙是人類最為常見感覺障礙之一,遺傳因素在聽力障礙致病因素中所占比例高達50%以上。耳聾基因的流行病學(xué)研究,不僅有利于揭示耳聾基因在人群中突變的流行病學(xué)特征,為耳聾疾病的早期診斷、早期干預(yù)、早期治療和遺傳咨詢提供理論和數(shù)據(jù)支持,而且關(guān)系到我國人口整體素質(zhì)的提高和國民經(jīng)濟的順利發(fā)展�？v觀近10年來對耳聾基因的流行病學(xué)研究發(fā)現(xiàn),國內(nèi)外在這類研究中都普遍存在的一個問題——不同研究數(shù)據(jù)結(jié)果差異性較大甚至相互矛盾。因此,為了準(zhǔn)確反映我國耳聾基因的流行病學(xué)特征,找出導(dǎo)致研究數(shù)據(jù)之間差異性的影響因素,本課題通過文獻回顧分析了目前我國耳聾基因流行學(xué)研究中存在的一些問題,并對我國大樣本非綜合征型感音神經(jīng)性耳聾(nonsyndromic sensorineural hearing loss, NSHL)人群進行分組對比研究,對不同分組樣本的常見核染色體耳聾基因GJB2和SLC26A4,以及線粒體DNA 12SrRNA A1555G (mitochondrial DNA 12SrRNA A1555G, mtDNAA1555G)的流行病學(xué)特征進行研究,不僅取得了不同來源和特征耳聾人群三種常見耳聾基因的流行病學(xué)數(shù)據(jù)資料,而且揭示了導(dǎo)致耳聾基因流行病學(xué)數(shù)據(jù)之間出現(xiàn)差異性的影響因素。本研究共分兩個部分： 第一部分耳聾基因突變流行病學(xué)研究現(xiàn)狀分析 本研究首先回顧了近10年來有關(guān)mtDNAA1555G、GJB2基因和SLC26A4基因突變的流行病學(xué)文獻,提出了目前這類研究中存在的主要問題——數(shù)據(jù)之間存在較大的差異性甚至矛盾。為了進一步探討導(dǎo)致這些差異性的原因,在第一部分第一章中我們檢索了1996年～2008年3月間報道的我國各地區(qū)mtDNAA1555G突變流行病學(xué)文獻資料,對每篇文獻中樣本量的選擇、樣本特征、地域分布、突變頻率特征及該突變與氨基糖甙類抗生素(aminoglycoside antibiotics, AmAn)應(yīng)用情況相互關(guān)系等多個因素進行分析。發(fā)現(xiàn)在國內(nèi)mtDNAA1555G突變頻率的流行病學(xué)調(diào)查中存在樣本選擇量不足、地區(qū)數(shù)據(jù)差異較大、缺少種族和年齡劃分等較多問題。其中樣本量差異可能是影響耳聾基因流行病學(xué)數(shù)據(jù)差異性的重要因素之一。因此在第二章中,采用嚴(yán)格的樣本量估計公式,選擇山東省NSHL耳聾人群進行mtDNA A1555G、GJB2和SLC26A4三種常見耳聾基因研究。在山東省485例患者中,mtDNAA1555G突變頻率為5.57%；GJB2致病突變頻率為24.12%,突變攜帶率為34.34%,高于多數(shù)的國內(nèi)報道；SLC26A4基因致病突變頻率為7.42%,突變攜帶率為13.61%。485名患者中有37.11%是由這三種基因突變導(dǎo)致的耳聾；推斷山東省約有2.45萬NSHL患者是由這三種基因突變所導(dǎo)致。 第二部分ntDNAA1555G,GJB2和SLC26A4基因流行病學(xué)數(shù)據(jù)影響因素研究 在本課題第二部分研究中,著重根據(jù)患者的來源和特征進行分組對比研究,對不同來源和特征的NSHL患者三種耳聾基因突變頻率進行比較,找出可能影響耳聾基因突變頻率的重要因素。在第一章研究中,發(fā)現(xiàn)mtDNAA1555G基因突變頻率會受到研究樣本中家系患者與散發(fā)患者數(shù)量比例,藥物性耳聾(aminoglucoside antibiotics induced deafness, AAID)患者與非AAID患者數(shù)量比例的影響。對于散發(fā)樣本來講,聾校與門診來源的患者數(shù)量比例變化也會影響到該基因突變頻率。在第二章研究中,發(fā)現(xiàn)GJB2基因突變頻率受到樣本中語前聾與語后聾患者數(shù)量比例的影響；對于散發(fā)樣本,聾校與門診來源的患者數(shù)量比例變化同樣也會影響到GJB2基因突變頻率。在第三章研究中,發(fā)現(xiàn)SLC26A4突變頻率相對于mtDNAA1555G和GJB2基因來講,受到更多因素的影響,研究樣本中家系患者與散發(fā)患者,語前聾患者與語后聾患者,門診患者與聾�；颊�,EVAS (enlarged vestibular aqueduct syndrome,EVAS)患者與非EVAS患者的樣本比例變化均是影響其數(shù)據(jù)結(jié)果的主要因素。 通過兩個部分的研究,本研究認為在耳聾致病基因的流行病學(xué)研究中,研究樣本的樣本量,樣本來源和特征等諸多因素影響著流行病學(xué)數(shù)據(jù)資料的準(zhǔn)確性。對不同基因來講,這些影響因素的作用效應(yīng)也是不同的。因此,為了準(zhǔn)確反映耳聾基因的流行病學(xué)特征,必須進行大樣本研究,根據(jù)不同的基因特征制定正確的符合流行病學(xué)要求的樣本納入標(biāo)準(zhǔn),確保樣本具有相同的來源和特征。只有這樣,才能有效避免研究數(shù)據(jù)之間出現(xiàn)差異性,保證研究結(jié)果的準(zhǔn)確性和穩(wěn)定性,為防聾治聾措施和策略的制定提供準(zhǔn)確的數(shù)據(jù)支持。
[Abstract]:Hearing impairment is one of the most common sensory disorders in human beings. The proportion of genetic factors in the pathogenic factors of hearing impairment is more than 50%. The epidemiological study of the deafness gene is not only helpful to reveal the epidemiological characteristics of the mutation of the deafness gene in the population, early diagnosis, early intervention, early treatment and genetic counseling for the deafness disease. The inquiry provides theoretical and data support, and is related to the improvement of the overall quality of our population and the smooth development of the national economy. An overview of the epidemiological studies of the deafness genes in the past 10 years has found that there is a common problem in this kind of research both at home and abroad - the differences in the results of different research data are large or even contradictory. In order to accurately reflect the epidemiological characteristics of the deafness genes in our country and find out the factors that lead to the difference between the research data, the subject through literature review and analysis of the existing problems in the current research of the deafness gene epidemiology in China, and the large sample of our country's non syndrome type sensorineural deafness (nonsyndromic sensorineural h) Earing loss, NSHL) group comparative study on the epidemiological characteristics of common nuclear chromosomal deafness genes, GJB2 and SLC26A4, and mitochondrial DNA 12SrRNA A1555G (mitochondrial DNA 12SrRNA A1555G), which not only obtained three common deafness in different sources and deafness groups. The epidemiological data of the gene and the factors that lead to the difference between the genetic epidemiological data of the deafness are revealed. This study is divided into two parts:
The first part is the analysis of the epidemiology of deafness gene mutation.
This study first reviewed the epidemiological literature about the mtDNAA1555G, GJB2 and SLC26A4 mutations in the last 10 years, and proposed the main problems in the present study - the large differences and even contradictions among the data. In order to further explore the causes of these differences, in the first chapter, we The epidemiological data of mtDNAA1555G mutation reported in various regions of China from 1996 to March 2008 were retrieved. The selection of sample size, sample characteristics, geographical distribution, mutation frequency characteristics and the relationship between the mutation and the application of aminoglycoside antibiotics (aminoglycoside antibiotics, AmAn) in each literature were carried out. Analysis. It is found that there are insufficient sample selection in the epidemiological survey of mtDNAA1555G mutation frequency in China. There are large differences in regional data and lack of race and age division. The difference in sample size may be one of the important factors affecting the difference of the deafness gene epidemiological data. Therefore, in the second chapter, it is strict. The NSHL deafness population of Shandong province was selected for the study of three common deafness genes of mtDNA A1555G, GJB2 and SLC26A4. In 485 cases of Shandong, the mutation frequency of mtDNAA1555G was 5.57%, the frequency of GJB2 pathogenic mutation was 24.12%, the mutation carrier rate was 34.34%, higher than the number of domestic reports, and the frequency of SLC26A4 gene mutation. For 7.42%, 37.11% of the patients with the mutation rate of 13.61%.485 were deafness caused by these three gene mutations; it was inferred that about 24 thousand and 500 NSHL patients in Shandong were caused by these three gene mutations.
The second part is about the factors affecting ntDNAA1555G, GJB2 and SLC26A4 genetic epidemiology data.
In the second part of this study, we focus on the comparison of the sources and characteristics of the patients, and compare the mutation frequencies of three kinds of deafness gene in NSHL patients with different sources and characteristics, and find out the important factors that may affect the frequency of the mutation of the deafness gene. In the first chapter, we found that the frequency of the mutation of the mtDNAA1555G gene will be subject to the frequency of mutation. The proportion of aminoglucoside antibiotics induced deafness (AAID) and non AAID patients in the sample of family and sporadic patients. For sporadic samples, the change in the number of patients from the deaf and outpatient sources also affects the mutation frequency of the gene. In the second chapter, It was found that the frequency of GJB2 gene mutation was affected by the proportion of pre lingual deafness and the number of post lingual deaf patients; for sporadic samples, the change in the number of patients in the deaf and outpatient sources also affected the frequency of GJB2 mutation. In the third chapter, the frequency conversion rate of SLC26A4 was found to be relative to the mtDNAA1555G and GJB2 genes. More factors are the main factors affecting the data results in the samples of family and sporadic patients, pre lingual deafness and post lingual deafness, outpatient and deaf patients, EVAS (enlarged vestibular aqueduct syndrome, EVAS) and non EVAS patients.
Two parts of the study suggest that in the epidemiological study of the deafness gene, the sample size, sample source and characteristics affect the accuracy of the epidemiological data. For different genes, the effects of these factors are different. Therefore, to accurately reflect deafness In order to ensure the accuracy and stability of the research results, the epidemiological characteristics of the gene must be studied in a large sample, and the correct samples of the epidemiological requirements are incorporated into the standard according to the different genetic characteristics to ensure that the samples have the same sources and characteristics. Accurate data support is necessary for formulating strategies and strategies for deafness prevention and treatment.

【學(xué)位授予單位】：中國人民解放軍軍醫(yī)進修學(xué)院
【學(xué)位級別】：博士
【學(xué)位授予年份】：2010
【分類號】：R764.43

【引證文獻】

相關(guān)期刊論文 前2條

1 賈金文;吳永祥;宋建濤;青霞;牟曉玄;;關(guān)于不同民族耳聾人群耳聾基因常見突變的篩查分析[J];生物技術(shù)世界;2014年05期

2 周黎紅;郝子琪;劉薇拉;馬云霞;任立宏;申靜;周永安;;GJB2基因V27I和E114G位點與耳聾相關(guān)性的研究[J];中國優(yōu)生與遺傳雜志;2012年12期

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本文編號：1851546