A duplication variant within middle-ear-specific gene A2ML1 co-segregates with otitis media in an indigenous Filipino pedigree (LOD score=7.5 at reduced penetrance) and lies within a founder haplotype that is also shared by three otitis-prone European- and Hispanic-American children, but is absent in non-otitis-prone children and >62,000 next-generation sequences. Seven additional A2ML1 variants were identified in six otitis-prone children. Collectively our studies support a role for A2ML1 in the pathophysiology of otitis media.

BackgroundPreviously rare A2ML1 variants were identified to confer otitis media susceptibility in an indigenous Filipino community and in otitis-prone US children. The goal of this study is to describe differences in the middle ear microbiome between carriers and non-carriers of an A2ML1 duplication variant that increases risk for chronic otitis media among indigenous Filipinos with poor health care access.MethodsEar swabs were obtained from 16 indigenous Filipino individuals with chronic otitis media, of whom 11 carry the A2ML1 duplication variant. Ear swabs were submitted for 16S rRNA gene sequencing.ResultsGenotype-based differences in microbial richness, structure, and composition were identified, but were not statistically significant. Taxonomic analysis revealed that the relative abundance of the phyla Fusobacteria and Bacteroidetes, and genus Fusobacterium were nominally increased in carriers compared to non-carriers, but were non-significant after correction for multiple testing. We also detected rare bacteria including Oligella that was reported only once in the middle ear.ConclusionsThese findings suggest that A2ML1-related otitis media susceptibility may be mediated by changes in the middle ear microbiome. Knowledge of middle ear microbial profiles according to genetic background can be potentially useful for therapeutic and prophylactic interventions for otitis media and can guide public health interventions towards decreasing otitis media prevalence within the indigenous Filipino community.Electronic supplementary materialThe online version of this article (doi:10.1186/s40249-016-0189-7) contains supplementary material, which is available to authorized users.

Objective To identify genetic and environmental risk factors for otitis media in an indigenous Filipino population Study Design Cross-sectional study Setting Indigenous Filipino community Subjects and Methods Clinical history and information on breastfeeding, tobacco smoke exposure and swimming were obtained from community members. Heads of households were interviewed for family history and personal beliefs on ear health. Height and weight were measured. Otoscopic findings were described for presence and character of perforation or discharge. An A2ML1 duplication variant that confers otitis media susceptibility was Sanger-sequenced in all DNA samples. Co-occurrence of middle ear bacteria detected by 16S rRNA gene sequencing was determined according to A2ML1 genotype and social cluster. Results The indigenous Filipino population has a ~50% prevalence of otitis media. Young age was associated with otitis media (4 age strata; p=0.004), however age was non-significant as a bi-stratal or continuous variable. There was no association between otitis media and gender, body mass index, breastfeeding, tobacco exposure or deep swimming. In multivariate analyses, A2ML1 genotype is the strongest predictor of otitis media, with an odds ratio of 3.7 (95%CI: 1.3, 10.8; p=0.005). When otitis media diagnoses were plotted across ages, otitis media was observed within the first year of life and chronic otitis media persisted up to adulthood, particularly in A2ML1 variant carriers. Conclusion Among indigenous Filipinos, A2ML1 genotype is the primary risk factor for otitis media and main determinant of disease progression, although age, the middle ear microbiome and social clusters might modulate the effect of the A2ML1 genotype.