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 i s 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 i nclude, 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.
