Genetic and Environmental Determinants of Otitis Media in an Indigenous Filipino Population

Abstract

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 the 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 = .004); however, age was nonsignificant as a bistratal or continuous variable. There was no association between otitis media and sex, 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% confidence interval: 1.3-10.8; P = .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.

Keywords: A2ML1; Philippines; indigenous population; microbiome; middle ear; otitis media.

Figure 1

Otitis media prevalence within indigenous Filipino population, which was relatively flat over 8 years. However there was a 6% increase in healed otitis media rates between 2011 and 2014 vs. 0–2% change in previous years.

Figure 2

Ear findings by age in years in (A) overall population, (B) A2ML1 carriers, and (C) wildtype individuals.

Figure 3

Indigenous Filipinos with 7 middle ear bacteria. For A2ML1: +, variant carriers; −, wildtype. Siblings from the same household are boxed. Connecting lines indicate individuals from the same age group, with threshold at 12.5 years.