Year: 2025
Type: article
Study design: Observational Study
Abstract: Otitis media is the most frequently diagnosed disease and a leading cause of hearing loss in young children. However, genetic contributors to susceptibility and pathogen–host–environment interactions in otitis media remain to be identified. Such knowledge would help identify at-risk individuals and effectively monitor, diagnose, and treat patients with otitis media. Through exome and Sanger sequencing, we identified a rare, deleterious splice variant SLPI c.394+1G>T co-segregating with otitis media in a large pedigree, with a genome-wide significant maximum LOD score of 4.59. Alternative splicing of SLPI was observed in saliva RNA of variant carriers. In bulk mRNA-seq data from an independent cohort of children with otitis media, SLPI was co-expressed with genes involved in infection, immune response, inflammation, and epithelial cell organization. After inoculation of non-typeable Haemophilus influenzae, Slpi was upregulated in polymorphonuclear leukocytes and epithelial cells of mouse middle ears. Furthermore, in the human middle ear, Haemophilus was significantly enriched in non-carriers, whereas Family-XI-Incertae-Sedis and Dialister were significantly enriched in variant carriers. Given the role of SLPI in immune modulation and host defense in mucosal epithelia, our findings support the SLPI variant as modulating susceptibility to otitis media.
DOI: 10.3390/ijms26041411
Authors: Christina L. Elling, Allen F. Ryan, Talitha Karisse L. Yarza, Amama Ghaffar, Erasmo Gonzalo d. V. Llanes, Jennifer M. Kofonow, Maria Rina T. Reyes-Quintos, Saima Riazuddin, Charles E. Robertson, Ma. Leah C. Tantoco, Zubair M. Ahmed, Abner L. Chan, Daniel N. Frank, Charlotte M. Chiong, Regie Lyn P. Santos-Cortez
Language: English
Topic: Ear Surgery and Otitis Media
Subfield: Otorhinolaryngology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,499
Funders: U.S. Department of Veterans Affairs, National Institutes of Health, National Heart, Lung, and Blood Institute, National Institute on Deafness and Other Communication Disorders, Fogarty International Center, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, National Institute of Environmental Health Sciences, National Center for Research Resources
Awards: G1017297203, G1082459641, G1284367791, Otitis Media Susceptibility and Middle Ear Microbial Shifts due to Gene Variants, G185653830, G2363836017, G2897333767, G3253097015, An Interdisciplinary Strategy for Obesity (RMI), Obesity development and CVD risk factor clustering in Filipino women & offspring, Effect of Health on Education &Work in Filipino Youth, G7716424844, G8446680376, G9000008043, G9000030607, G9000047336, G9000098965, G9000120765, G9000144966, G9000150906, G9000189352, G9000190511, G9000265623, Genetics and Functional Studies of Autosomal Recessive Neurological Disorders, UNC Center for Environmental Health and Susceptibility, Nutrition Obesity Research Center (NORC), Genetic and epigenomic determinants of hearing loss in Hispanic populations
OpenAlex ID: W4407253530