GENETIC EPIDEMIOLOGY OF CHRONIC/RECURRENT OTITIS MEDIA

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。本研究的长期目标是寻找参与慢性/复发性中耳炎（COME/ROM）发展的一个或多个基因，并确定在这些疾病易感性中发挥作用的任何基因-基因或基因-环境相互作用。发现与COME/ROM易感性相关的基因将为疾病的发病机制和病因机制提供深入了解，从而提出新的治疗和预防策略。有了遗传易感性的知识，高危儿童可以有针对性地进行严格的监测和积极的治疗，以防止COME/ROM后遗症，包括听力损失。如果针对具有明确遗传风险的儿童，初级预防战略可能会更有效。本研究旨在证明在整个人类基因组中COME/ROM和多态性DNA标记之间的家族连锁。该研究旨在确定至少有两个兄弟姐妹的家族中的基因型，这些兄弟姐妹有COME/ROM的证据（通过病史，耳部检查，多频鼓室压测试和医疗记录确定），以及一个受影响和一个未受影响的兄弟姐妹的家族。从几项先证者接受试管治疗的研究中招募了家庭成员。来自133个家庭（153个受影响的同胞对，138个不一致的同胞对和95个受影响的亲属对）的总共591个DNA样本在遗传疾病研究中心（CIDR）进行了400个标记基因组筛选。分析显示与COME/ROM在3号、10号和19号染色体上存在显著连锁。目前正在对基因组筛查中确定的连锁区域进行重点评价，包括密集遗传图谱、候选基因分析和招募800例无关病例和对照进行关联分析，并复制家族研究结果。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The long-term goal of this study is to find a gene or genes involved in the development of chronic/recurrent otitis media (COME/ROM) and to identify any gene-gene or gene-environment interactions that play a role in the susceptibility to these conditions. Discovery of genes linked to COME/ROM susceptibility will provide insight into disease pathogenesis and etiologic mechanisms, thereby suggesting new treatment and prevention strategies. With knowledge of genetic susceptibility, high-risk children could be targeted for rigorous surveillance and aggressive treatment to prevent COME/ROM sequelae including hearing loss. Primary prevention strategies could be more efficient if they targeted children with defined genetic risk. This study is designed to demonstrate linkage in families between COME/ROM and polymorphic DNA markers across the entire human genome. The study aims to determine genotypes in families with at least two siblings with evidence of COME/ROM (ascertained by history, ear examination, multifrequency tympanometry, and medical record), and in families with one affected and one unaffected sibling. Families were recruited from several studies in which the proband was treated with tubes. A total of 591 DNA samples from 133 families (153 affected sib pairs, 138 discordant sib pairs and 95 affected relative pairs) underwent a 400 marker genome screen at the Center for Inherited Disease Research (CIDR). Analysis revealed significant linkage with COME/ROM at chromosome 3, 10, and 19. Focused evaluation of areas of linkage identified in the genome screen with dense genetic mapping, candidate gene analyses, and recruitment of 800 unrelated cases and controls for association analyses is and replication of family study results is ongoing.