PRESBYCUSIS--BIOMEDICAL RISK FACTORS

老年痴呆症--生物医学风险因素

• 批准号: 6175508
• 负责人: George A. Gates
• 金额: $ 36.44万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-07-01 至 2002-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6175508
• 关键词: aging; audiometry; auditory threshold; clinical research; disease /disorder onset; disease /disorder proneness /risk; epidemiology; estrogens; family genetics; gender difference; gene environment interaction; genetic registry /resource /referral center; genetic susceptibility; hearing tests; human genetic material tag; human subject; linkage mapping; otoacoustic emission; parents; phenotype; presbycusis

Presbycusis - age-related hearing loss - is an increasingly common communication disorder due to the aging and noisiness of our society.The prevalence and severity of presbycusis vary substantially in people of the same age and gender but the source(s) of this variability are incompletely understood. A major putative factor for this variability is heredity. The proposed research will continue our study of presbycusis using comprehensive examination methods to determine the inheritability of presbycusis in relation to its epidemiology and biomedical risk factors. We propose to: a) finish the auditory testing of the targeted members of the Framingham Offspring Group to determine the prevalence of presbycusis (as for their parents; b) delineate clinical presbycusis phenotypes in both groups; c) perform quantitative linkage analysis using the existing Genescan data base for the families with presbycusis pedigrees, d) perform complex segregation analysis of presbycusic families to assess the Mendelian inheritance patterns; and e) identity risk factors in families with genetic transmission. This is the first modern human study to assess the heritability of presbycusis. State-of-the-art methodology for auditory testing and genetic epidemiology are used. This research can only be done in a large parent-offspring group such as the Framingham Heart Study. Because the parents' hearing testing is done, and about 2/3 of the target Offspring will have been tested under the current funding, completion of this project will require testing of the remaining target Offspring during the first part of Offspring Study 7. Auditory tests are unchanged: pure-tone thresholds, immittance audiometry, acoustic impedance and reflectance, otoacoustic emissions, word recognition in quiet, Dichotic Digits test and the Synthetic Sentence Identification with Ipsilateral Competing Message. Presbycusis will be coded by: a) age-adjusted severity of loss; b) clinical pattern and phenotype, and c) whether it is of an early-onset type or not. Quantitative linkage analysis in the Genescan data base will examine the DNA of large families with presbycusis. Segregation analysis will be done for different phenotypes defined as: a) severity of presbycusis, b) presbycusis pattern, c) early-onset presbycusis, and d) co-variate adjusted models that will include known risk factors (gender, noise exposure, and cardiovascular diseases). Characterizing presbycusis by severity, age of onset, and clinical subtype will help to identify specific risk factors associated with hereditary presbycusis among genetically predisposed individuals. Identification of families with inherited presbycusis will facilitate future molecular genetic studies to identify genes for inherited defects.

老年性耳聋（Presbycusis）是一种与年龄相关的听力损失，由于社会的老龄化和噪音，老年性耳聋是一种越来越常见的交流障碍。老年性耳聋的患病率和严重程度在相同年龄和性别的人群中有很大差异，但这种差异的来源并不完全清楚。这种变异性的一个主要假定因素是遗传。拟议的研究将继续我们的研究，老年性耳聋使用全面的检查方法，以确定老年性耳聋的遗传性与其流行病学和生物医学危险因素。我们建议：a）完成对弗雷明汉后代小组目标成员的听力测试，以确定老年性聋的患病率（B）描述两组老年性耳聋的临床表型，（c）利用已有的Genescan数据库对老年性耳聋家系进行定量连锁分析，（d）对老年性耳聋家系进行复杂分离分析，以评估孟德尔遗传模式;及e）找出有遗传传播的家庭的危险因素。这是第一个现代人类研究评估老年性耳聋的遗传性。国家的最先进的听觉测试和遗传流行病学的方法。这项研究只能在一个大型的亲子组中进行，如心脏病研究。由于父母的听力测试已经完成，并且在目前的资助下，大约2/3的目标后代将接受测试，因此完成该项目将需要在后代研究7的第一部分期间对剩余的目标后代进行测试。听力测试保持不变：纯音听阈、导抗测听、声阻抗和反射、耳声发射、安静条件下的单词识别、双耳分音数字试验和同侧竞争信息合成句识别。将通过以下方式对老年性耳聋进行编码：a）年龄调整的听力丧失严重程度; B）临床模式和表型;以及c）是否为早发型。基因扫描数据库中的定量连锁分析将检查老年性耳聋大家族的DNA。将对定义为以下的不同表型进行分离分析：a）老年性耳聋的严重程度，B）老年性耳聋模式，c）早发性老年性耳聋，以及d）包括已知风险因素（性别、噪声暴露和心血管疾病）的协变量校正模型。根据严重程度、发病年龄和临床亚型来描述老年性耳聋的特征将有助于在遗传易感个体中识别与遗传性老年性耳聋相关的特定危险因素。遗传性老年性耳聋家系的鉴定将有助于未来的分子遗传学研究，以确定遗传缺陷的基因。