Genetic Epidemiology of Chronic/Recurrent Otitis Media

描述(申请人提供)：这项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，以增进对其潜在的生物学和病理机制的了解。这将有助于制定更有效的预防和治疗战略，包括以高危儿童为目标进行严格监测，并制定预防和积极治疗战略，以防止COMP/ROM及其后遗症。这是初始资助期的延续，在此期间完成了系谱确定、招募和广泛的表型评估，并进行了基因组扫描。基因组的区域被确定为包含导致COME/ROM风险的数量性状基因座(QTL)，候选基因分析显示FBXO11(杰夫小鼠模型基因的人类同源物)的多态与COME/ROM之间存在关联。第一个目标是对我们之前的基因组扫描分析中确定的染色体区域10q26、19q13.4和3p24-25进行有针对性的连锁研究，重点是10q26区域。这一精细定位的结果将被用于识别连锁峰，以便进行详细的分子遗传分析。其他目标包括，2)继续招募无关的、特征明确的病例和对照，以促进关联和不平衡作图，以便与基于家庭的分析相比较；3)使用高密度SNP图谱，系统地搜索高质量连锁高峰下的Come/ROM与基因和/或单倍型块之间的关联，并使用集中的SNP基因分型和基于家系的关联分析，在家系集合中探索一系列支持与Come/ROM连锁的位置候选基因；以及4)通过对家系和病例和对照中与Come/ROM相关的基因和/或单倍型块进行详细分析，来识别Come/ROM易感基因。病例和对照将从以下方面招募：明尼苏达大学的学生群体、有大量少数民族入学的技校和大学、以前的中耳炎研究，以及在明尼苏达大学接受耳鼻喉科手术的儿童。参与者将参加一个研究访问，其中包括收集表型数据和DNA样本。预计这项研究将为基因-基因和基因-环境的相互作用提供新的见解，这些因素有助于儿童COMe/ROM的发展。

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.