Noise-Induced Hearing Loss: Threshold, exposure and genetic susceptibility

噪声性听力损失：阈值、暴露程度和遗传易感性

• 批准号: 7990687
• 负责人: SUSAN L PHILLIPS
• 金额: $ 20.97万
• 依托单位: UNIVERSITY OF NORTH CAROLINA GREENSBORO
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-28 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7990687
• 关键词: Accreditation; Acoustics; Age; Aging; Alleles; Audiology; Audiometry; Bilateral; Candidate Disease Gene; Caring; Cells; Characteristics; Chemical Exposure; Chemicals; Child; Clinical; Collection; Confounding Factors (Epidemiology); Control Groups; DNA; Data; Development; Devices; Disease; Doctor of Philosophy; Ear; Education; Educational Curriculum; Environmental Exposure; Exposure to; Extreme Hearing Loss; Frequencies; General Population; Genes; Genetic; Genetic Polymorphism; Genetic Predisposition to Disease; Genetic Variation; Genetic screening method; Genotype; Goals; Health; Health Personnel; Healthcare; Hearing; Human Genetics; Incidence; Individual; Industrial Arts; Ion Channel; Knowledge; Measurement; Measures; Methods; Military Personnel; Modification; Monitor; Music; Myristica fragrans; Noise; Noise-Induced Hearing Loss; Other Genetics; Oxidative Stress; Phase; Phenotype; Population; Predisposition; Presbycusis; Prevalence; Prevention program; Prevention strategy; Preventive; Preventive Intervention; Proteins; Public Health; Public Policy; Reporting; Research; Research Personnel; Research Project Grants; Resistance; Risk; SOD2 gene; Schools; Site; Smoking; Specialist; Students; Teenagers; Testing; Training; Translational Research; Universities; Variant; Work; aged; attenuation; base; catalase; college; experience; gene environment interaction; genetic association; hearing impairment; human CDH23 protein; human GJB2 protein; improved; innovation; kindergarten; musician; notch protein; programs; public health relevance; sound; statistics; teacher; university student; young adult

DESCRIPTION (provided by applicant): The short-term goal of this R21 Translational Research Grant PAR 06-095 application, entitled "Noise-induced hearing loss: threshold, exposure, and genetic susceptibility," is to establish a basis for identifying people showing a genetic susceptibility to noise-induced hearing loss (NIHL). The application is proposed by a team of three researchers: The PI is Susan L. Phillips, Ph.D. in audiology (CCC-A), who is working with Co-PI's Vincent C. Henrich, Ph.D. in genetics, Scott J. Richter, Ph.D. in statistics and Sandra T. Mace, Ph.D. in music education and certified Hearing Conservation Specialist. It is known that acoustic overexposure can cause noise-induced hearing loss. Nevertheless, there is considerable variability in NIHL even among subjects who have not experienced unusual levels of acoustic exposure, and, thus, there is a critical gap in our knowledge about who is and is not most at risk for NIHL. This project will fill the gap in knowledge by identifying the critical variables associated with a genetic predisposition to NIHL. Critical variables identified in our study so far include the audiological profile (unilateral or bilateral, depth of notch and frequency of notch), reported current and past acoustic exposure and measured acoustic exposure (intensity and duration). The Specific Aims are: 1) Compare the crude and adjusted prevalence among subjects with bilateral, unilateral, or no notches of variants at several gene loci found in previous research to be associated with NIHL. Based on criteria laid out in Phillips et al. (in press), the working hypothesis will be that the frequency of predisposing alleles for NIHL will be higher among individuals with bilateral notches than in those with unilateral or no notches. 2) Examine whether there are significant gene-environment interactions present. The working hypothesis will be that the individuals with the highest current exposure and carrying predisposing alleles to NIHL will show the greatest progression of NIHL. We will make direct and indirect measurements of thresholds and exposure levels in a study involving 1,000 students between the ages of 18-25 years, allowing us to avoid the confounds present in other genetic association studies of NIHL. These include age-related hearing loss and disease factors that can contribute to hearing loss, additional chemical exposures that can contribute to hearing loss, and the extreme exposures and exposure durations associated with industrial populations. Previous studies have found it necessary to apply statistical corrections for these confounds and the corrections were acknowledged to have complicated the interpretation of the data (Konings et al., 2009). Buccal cells will be collected and DNA extracted from students in three groups: those with bilateral notches, with unilateral notches, and a control group of students with no notches. The project's relevance to public health is reflected in our long-term goal, which is to use a mechanistic understanding of NIHL to develop a personalized NIHL prevention program using standard clinical audiological tests as indicators of genetic susceptibility. The ability to identify at-risk individuals and exposure situations at an early age, perhaps through the development of a NIHL Risk Profile, will allow health care providers, music educators, industrial and military hearing conservationists, and others to target preventive measures to at-risk individuals. Preventive measures include education, the use of hearing protection devices, sound attenuation modifications to exposure sites and monitoring of exposure intensities and durations. PUBLIC HEALTH RELEVANCE: NIHL is a growing health concern among children, found in 15.5% aged 12-19 (Niskar et al., 2001), in 28% of college students who listen to personal listening devices (Mostafpour et al., 1998), and 44% of student musicians in a university School of Music (Phillips et al., in press). The short-term goal of this application for an R21 Translational Research Grant PAR 06-095, entitled "Noise-induced hearing loss: threshold, exposure, and genetic susceptibility," is to establish a basis for identifying people showing a genetic susceptibility to noise-induced hearing loss. The relevance of the project to public health is reflected in the long-term goal, which is to use a mechanistic understanding of noise-induced hearing loss to develop a personalized prevention program using standard clinical audiological tests as indicators of genetic susceptibility.

描述（由申请人提供）：这项R21转化研究资助PAR 06-095申请的短期目标，题为“噪声引起的听力损失：阈值，暴露和遗传易感性”，是建立一个基础，用于识别对噪声引起的听力损失（NIHL）表现出遗传易感性的人。该应用程序是由三名研究人员组成的团队提出的：PI是Susan L。菲利普斯博士在听力学（CCC-A），谁是合作PI的文森特C。Henrich博士Scott J. Richter，Ph.D.在统计学和桑德拉T。梅斯博士音乐教育和认证的听力保护专家。众所周知，声学过度可导致噪声引起的听力损失。然而，即使在没有经历过异常水平的声学暴露的受试者中，NIHL也存在相当大的差异，因此，我们对谁是NIHL风险最大的人的知识存在重大差距。这个项目将填补知识的差距，确定与遗传易感性NIHL的关键变量。到目前为止，我们的研究中确定的关键变量包括听力学特征（单侧或双侧，切迹深度和切迹频率），报告的当前和过去的声学暴露和测量的声学暴露（强度和持续时间）。具体目标是：1）比较在先前研究中发现的与NIHL相关的几个基因位点上具有双侧、单侧或无突变的受试者的粗患病率和校正患病率。根据菲利普斯等人（出版中）提出的标准，工作假设是，双侧切口的个体中NIHL易感等位基因的频率高于单侧或无切口的个体。2)检查是否存在显著的基因-环境相互作用。工作假设是，当前暴露量最高且携带NIHL易感等位基因的个体将显示NIHL的最大进展。我们将在一项涉及1,000名年龄在18-25岁之间的学生的研究中直接和间接测量阈值和暴露水平，使我们能够避免其他NIHL遗传关联研究中存在的混淆。这些因素包括与年龄相关的听力损失和可能导致听力损失的疾病因素，可能导致听力损失的额外化学品暴露，以及与工业人口相关的极端暴露和暴露时间。先前的研究已经发现有必要对这些混淆应用统计校正，并且承认校正使数据的解释复杂化（Konings等人，2009年）。颊细胞将被收集，并从三组学生中提取DNA：那些双边缺口，与单边缺口，和一个控制组的学生没有缺口。该项目与公共卫生的相关性反映在我们的长期目标中，即使用对NIHL的机械理解，使用标准临床听力学测试作为遗传易感性指标，制定个性化的NIHL预防计划。在早期识别风险个体和暴露情况的能力，也许通过开发NIHL风险简介，将允许医疗保健提供者，音乐教育工作者，工业和军事听力保护者以及其他人针对风险个体采取预防措施。预防措施包括教育、使用听力保护装置、对接触地点进行声音衰减调整以及监测接触强度和持续时间。 公共卫生相关性：NIHL是儿童中日益增长的健康问题，在12-19岁的15.5%中发现（Niskar等人，2001年），在28%的大学生谁听个人听力设备（Mostafpour等人，1998年），和44%的学生音乐家在大学音乐学院（菲利普斯等人，印刷中）。这项R21转化研究资助PAR 06-095申请的短期目标，题为“噪声引起的听力损失：阈值，暴露和遗传易感性”，是建立一个基础，用于识别对噪声引起的听力损失表现出遗传易感性的人。该项目与公共卫生的相关性反映在长期目标中，即利用对噪音引起的听力损失的机械性理解，利用标准临床听力学测试作为遗传易感性指标，制定个性化的预防计划。