GENETIC EPIDEMIOLOGY OF CHRONIC/RECURRENT OTITIS MEDIA

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。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。列出的机构是 中心，不一定是研究者的机构。 本研究的目的是证明和确认遗传因素在慢性渗出性中耳炎和复发性中耳炎（COME/ROM）发展中的作用，以提高对其潜在生物学和病理学机制的理解。这将有助于制定更有效的预防和治疗策略，包括针对高危儿童进行严格的监测，并制定预防和积极的治疗策略，以预防COME/ROM及其后遗症。 这是初始资助期的延续，在此期间完成了谱系确定、招募和广泛的表型评估，并进行了基因组扫描。基因组区域被确定为含有数量性状基因座（QTL），有助于风险 的COME/ROM，和候选基因分析显示， FBXO 11（Jeff小鼠模型基因的人类同源物）中的多态性，以及 在本报告所述期间，我们正在进行有针对性的联系， 对10号、19号和3号染色体的研究， 家庭收藏。精细映射的结果将用于识别 连锁峰进行详细的分子遗传分析。我们还将继续 招募无关的、特征明确的病例和对照进行关联研究，以与基于家族的分析进行比较，并在家族集合中探索支持与COME/ROM连锁的一系列候选基因 使用聚焦SNP基因分型和基于家族的关联分析。将通过对家族和病例及对照中与COME/ROM相关的基因和/或单倍型区块进行详细分析，鉴定COME/ROM易感基因。预计这项研究将提供新的见解基因-基因和基因-环境的相互作用，有助于COME/ROM的发展在儿童时期。

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 goals of this study are to demonstrate and confirm the role of genetic factors in the development of chronic otitis media with effusion and recurrent otitis media (COME/ROM) to improve understanding of its underlying biological and pathological mechanisms. This will enable development of more effective prevention and treatment strategies,including targeting high risk children for rigorous surveillance and developing prevention and aggressive treatment strategies to prevent COME/ROM and its sequelae. This is the continuation of an initial funding period during which pedigree ascertainment, recruitment, and extensive phenotypic assessment was completed, and a genome scan performed. Regions of the genome were identified that contain quantitative trait loci (QTLs) contributing to risk of COME/ROM, and candidate gene analyses revealed an association between polymorphisms in FBXO11, the human homolog of the Jeff mouse model gene, and COME/ROM. During the current period, we are performing targeted linkage studies on chromosomes 10, 19 and 3 identified in the genome scan of the family collection. Results of the fine mapping will be used to identify a linkage peak for detailed molecular genetic analysis. We will also continue to recruit unrelated, well characterized cases and controls for association studies to compare with family-based analysis and explore a series of candidate genes supporting linkage to COME/ROM in the family collection using focused SNP genotyping and family-based association analysis. COME/ROM susceptibility genes will be identified by performing a detailed analysis of genes and/or haplotype blocks associated with COME/ROM in both families and cases and controls. It is anticipated that this study will provide new insights into the gene-gene and gene-environment interactions that contribute to the development of COME/ROM in childhood.