中国耳聋人群常见基因分子流行病学特征及其影响因素的研究

发布时间：2018-05-06 08:28

本文选题：基因 + 耳聋　；参考：《中国人民解放军军医进修学院》2010年博士论文

【摘要】： 听力障碍是人类最为常见感觉障碍之一,遗传因素在听力障碍致病因素中所占比例高达50%以上。耳聋基因的流行病学研究,不仅有利于揭示耳聋基因在人群中突变的流行病学特征,为耳聋疾病的早期诊断、早期干预、早期治疗和遗传咨询提供理论和数据支持,而且关系到我国人口整体素质的提高和国民经济的顺利发展。纵观近10年来对耳聋基因的流行病学研究发现,国内外在这类研究中都普遍存在的一个问题——不同研究数据结果差异性较大甚至相互矛盾。因此,为了准确反映我国耳聋基因的流行病学特征,找出导致研究数据之间差异性的影响因素,本课题通过文献回顾分析了目前我国耳聋基因流行学研究中存在的一些问题,并对我国大样本非综合征型感音神经性耳聋(nonsyndromic sensorineural hearing loss, NSHL)人群进行分组对比研究,对不同分组样本的常见核染色体耳聋基因GJB2和SLC26A4,以及线粒体DNA 12SrRNA A1555G (mitochondrial DNA 12SrRNA A1555G, mtDNAA1555G)的流行病学特征进行研究,不仅取得了不同来源和特征耳聋人群三种常见耳聋基因的流行病学数据资料,而且揭示了导致耳聋基因流行病学数据之间出现差异性的影响因素。本研究共分两个部分：第一部分耳聋基因突变流行病学研究现状分析本研究首先回顾了近10年来有关mtDNAA1555G、GJB2基因和SLC26A4基因突变的流行病学文献,提出了目前这类研究中存在的主要问题——数据之间存在较大的差异性甚至矛盾。为了进一步探讨导致这些差异性的原因,在第一部分第一章中我们检索了1996年～2008年3月间报道的我国各地区mtDNAA1555G突变流行病学文献资料,对每篇文献中样本量的选择、样本特征、地域分布、突变频率特征及该突变与氨基糖甙类抗生素(aminoglycoside antibiotics, AmAn)应用情况相互关系等多个因素进行分析。发现在国内mtDNAA1555G突变频率的流行病学调查中存在样本选择量不足、地区数据差异较大、缺少种族和年龄划分等较多问题。其中样本量差异可能是影响耳聋基因流行病学数据差异性的重要因素之一。因此在第二章中,采用严格的样本量估计公式,选择山东省NSHL耳聋人群进行mtDNA A1555G、GJB2和SLC26A4三种常见耳聋基因研究。在山东省485例患者中,mtDNAA1555G突变频率为5.57%；GJB2致病突变频率为24.12%,突变携带率为34.34%,高于多数的国内报道；SLC26A4基因致病突变频率为7.42%,突变携带率为13.61%。485名患者中有37.11%是由这三种基因突变导致的耳聋；推断山东省约有2.45万NSHL患者是由这三种基因突变所导致。第二部分ntDNAA1555G,GJB2和SLC26A4基因流行病学数据影响因素研究在本课题第二部分研究中,着重根据患者的来源和特征进行分组对比研究,对不同来源和特征的NSHL患者三种耳聋基因突变频率进行比较,找出可能影响耳聋基因突变频率的重要因素。在第一章研究中,发现mtDNAA1555G基因突变频率会受到研究样本中家系患者与散发患者数量比例,药物性耳聋(aminoglucoside antibiotics induced deafness, AAID)患者与非AAID患者数量比例的影响。对于散发样本来讲,聋校与门诊来源的患者数量比例变化也会影响到该基因突变频率。在第二章研究中,发现GJB2基因突变频率受到样本中语前聋与语后聋患者数量比例的影响；对于散发样本,聋校与门诊来源的患者数量比例变化同样也会影响到GJB2基因突变频率。在第三章研究中,发现SLC26A4突变频率相对于mtDNAA1555G和GJB2基因来讲,受到更多因素的影响,研究样本中家系患者与散发患者,语前聋患者与语后聋患者,门诊患者与聋校患者,EVAS (enlarged vestibular aqueduct syndrome,EVAS)患者与非EVAS患者的样本比例变化均是影响其数据结果的主要因素。通过两个部分的研究,本研究认为在耳聋致病基因的流行病学研究中,研究样本的样本量,样本来源和特征等诸多因素影响着流行病学数据资料的准确性。对不同基因来讲,这些影响因素的作用效应也是不同的。因此,为了准确反映耳聋基因的流行病学特征,必须进行大样本研究,根据不同的基因特征制定正确的符合流行病学要求的样本纳入标准,确保样本具有相同的来源和特征。只有这样,才能有效避免研究数据之间出现差异性,保证研究结果的准确性和稳定性,为防聋治聋措施和策略的制定提供准确的数据支持。
[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.

【学位授予单位】：中国人民解放军军医进修学院
【学位级别】：博士
【学位授予年份】：2010
【分类号】：R764.43

【引证文献】