Genetic Epidemiology of Chronic/Recurrent Otitis Media

描述（由申请人提供）：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。基因组的区域被鉴定为包含有助于COME/ROM风险的数量性状基因座（QTL），候选基因分析揭示了FBXO 11（Jeff小鼠模型基因的人类同源物）中的多态性与COME/ROM之间的关联。第一个目的是对染色体区域10 q26进行靶向连锁研究，19q13.4和3 p24 -25在我们以前的基因组扫描分析中使用家庭收集，重点是10 q26区域。这一精细定位的结果将被用来确定详细的分子遗传分析的连锁峰。其他目的包括，2）继续招募无关的、充分表征的病例和对照，以促进关联和不平衡作图，用于与基于家族的分析进行比较，3）使用高密度SNP图谱系统地搜索COME/ROM与高质量连锁峰下的基因和/或单倍型块之间的关联，并使用聚焦SNP基因分型和基于家族的关联分析在家族集合中探索支持与COME/ROM连锁的一系列位置候选基因，和4）通过对家族和病例及对照中与COME/ROM相关的基因和/或单倍型块进行详细分析来鉴定COME/ROM易感基因。病例组和对照组将从以下人群中招募：明尼苏达大学的学生团体、少数民族入学的技术学校和学院、先前的中耳炎研究以及在明尼苏达大学接受耳鼻喉科手术的儿童。参与者将参加研究访视，包括收集表型数据和DNA样本。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，有助于发展COME/ROM在儿童时期。

DESCRIPTION (provided by applicant): 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. The first aim is to perform targeted linkage studies on chromosomal regions 10q26,19q13.4 and 3p24-25 identified in our previous genome scan analysis using the family collection, with emphasis on the 10q26 region. Results of this fine mapping will be used to identify a linkage peak for detailed molecular genetic analysis. Other aims include, 2) continuing to recruit unrelated, well characterized cases and controls to facilitate association and disequilibrium mapping for comparison with family-based analysis, 3) searching systematically for an association between COME/ROM and genes and/or haplotype blocks under the high quality linkage peak using a high density SNP map, and exploring a series of positional candidate genes supporting linkage to COME/ROM in the family collection using focused SNP genotyping and family-based association analysis, and 4) identifying COME/ROM susceptibility genes by performing a detailed analysis of genes and/or haplotype blocks associated with COME/ROM in both families and cases and controls. Cases and controls will be recruited from: the student body at the U of MN, technical schools and colleges with substantial minority enrollment, previous studies of otitis media, and children undergoing otolaryngologic surgery at the U of MN. Participants will attend a study visit that includes collection of phenotypic data and DNA samples. 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.