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中耳炎积液和复发性中耳炎（COME/ROM）发展中的作用，以提高对其潜在生物学和病理机制的理解。这将有助于制定更有效的预防和治疗战略，包括针对高风险儿童进行严格监测，并制定预防和积极治疗战略，以预防COME/ROM及其后遗症。这是最初资助期的延续，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。基因组的一些区域被鉴定出含有与COME/ROM风险相关的数量性状位点（qtl），候选基因分析揭示了FBXO11多态性（Jeff小鼠模型基因的人类同源基因）与COME/ROM之间的关联。第一个目标是对我们之前使用家族收集的基因组扫描分析中发现的染色体区域10q26、19q13.4和3p24-25进行靶向连锁研究，重点是10q26区域。这种精细定位的结果将用于确定一个连锁峰，以进行详细的分子遗传分析。其他目标包括：2)继续招募不相关的、特征良好的病例和对照，以促进关联和不平衡定位，以便与基于家庭的分析进行比较；3)使用高密度SNP图系统地搜索高质量连锁峰下的COME/ROM与基因和/或单倍型块之间的关联；并利用重点SNP基因分型和基于家族的关联分析，探索家族收集中支持COME/ROM连锁的一系列位置候选基因。4)通过对两个家族、病例和对照中与COME/ROM相关的基因和/或单倍型块进行详细分析，确定COME/ROM易感基因。病例和对照组将从以下人群中招募：明尼苏达大学的学生群体，少数民族入学的技术学校和学院，以前的中耳炎研究，以及在明尼苏达大学接受耳鼻喉外科手术的儿童。参与者将参加研究访问，包括收集表型数据和DNA样本。预计本研究将为儿童COME/ROM的基因-基因和基因-环境相互作用提供新的见解。

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.