AbstractObjectives/Hypothesis.Mucin genes MUC2, MUC5AC, and MUC5B have been identified as major gel‐forming mucins in the middle ear (ME). This study compared polymorphisms in MUC2, MUC5AC, and MUC5B genes in otitis media (OM) patients and controls.Study Design.Cross‐sectional case‐control study. Patients age 6 months to 14 years undergoing routine tympanostomy tube insertion for recurrent otitis media (RecOM) or chronic otitis media with effusion (OME) were compared to control patients with no history of OM undergoing an unrelated procedure.Methods.Genomic DNA extracted from peripheral blood samples was analyzed by Southern blots using gene‐specific probes to determine sizes of MUC2 and MUC5AC genes. Polymerase chain reaction was used to determine the size of MUC5B genes.Results.Twenty RecOM patients, 20 OME patients, and 40 control patients were analyzed. There were no statistically significant differences in polymorphism expression identified between groups for MUC2 and MUC5B genes. OME patients were more likely than controls or RecOM patients to carry the longer MUC5AC‐b allele.Conclusions.Differences in mucin polymorphisms have been demonstrated in other diseases. In otitis media, OME patients are more likely than controls or RecOM to carry the longer MUC5AC‐b allele. MUC5AC is a primary innate defense mechanism for ME epithelium, and alterations in protein structure have the potential to affect that defense and predispose patients to disease. This study demonstrates that the properties of post‐transcriptionally modified MUC5AC deserve further study, and specific pathogen‐host interactions studies should explore the impact of this polymorphism. Laryngoscope, 2010