A novel high-throughput analysis approach: immune response-related genes are upregulated in age-related hearing loss
Yolande Tra1, Robert D Frisina2, Mary D'Souza3
1MD Poison Center, School of Pharmacy, University of Maryland, Baltimore, MD, 2Department of Chemical and Biomedical Engineering, College of Engineering, University of South Florida, Tampa FL, 3Department of Surgery, and the Wilmot Cancer Center, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA
Background: Presbycusis is defined as the hearing loss that occurs with aging. Genes that are responsible for this clinical condition have still not been identified. The present study explores gene discovery for age-related hearing loss using the CBA/CaJ mouse model of age-related hearing loss.
Methods and results: In the present investigation, in addition to a gene-based analysis, a molecular pathway analysis was performed to evaluate differences in gene expression in 15 aged mice with age-related hearing loss, and 25 young to middle-aged mice with normal hearing. Using three different statistical approaches, the gene-based analysis revealed four common probe sets, ie, Ctss (Cathespin), Csnk (casein kappa), Mpeg1 (macrophage-expressed gene 1), and Clecsf12 (C-type calcium-dependent carbohydrate recognition domain lectin, superfamily member 12) that are significantly upregulated with age and hearing loss in the mouse cochlea (inner ear). Relative real-time polymerase chain reaction was used for quantitative, sensitivity analysis of gene transcription changes and confirmed the gene microarray results. Three strategies for pathway analysis were consistent with these gene expression discoveries, and revealed a common immune response pathway. More specifically, the analysis suggests that B cell-mediated humoral immune function plays an important role in the underlying etiology of presbycusis, similar to certain other neurodegenerative diseases. Other top pathways from this analysis included those involving dendritic antigen-presenting cells, carbohydrate binding, G-protein coupled receptor binding, and epithelial-to-mesenchymal transition pathways.
Conclusion: Combining microarray gene discovery, polymerase chain reaction, and multiple pathway analyses revealed insights into immune system involvement in the progression of age-related hearing loss.
Keywords: high-throughput gene analysis, gene microarray, presbycusis, bioinformatics, biostatistics, auditory system
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