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 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.

A2ML1and otitis media: novel variants, differential expression, and relevant pathways

“…In mixed models analysis, in which family branch or household was analyzed as a random effect, otitis media was associated with both gingivitis ( p = 0.0007) and A2ML1 variants ( p = 0.048). Neither age nor sex was associated with otitis media, consistent with previous findings (Santos‐Cortez, Reyes‐Quintos et al, ).…”

“…Our previous discovery of A2ML1 (MIM 610627), which encodes alpha‐2‐macroglobulin‐like‐1, as an autosomal dominant gene for otitis media susceptibility suggested that rare variants play a role in otitis media pathology (Santos‐Cortez et al, ). An indigenous Filipino population with an approximately 50% prevalence of otitis media was found to have an A2ML1 duplication variant as the strongest predictor for disease (Santos‐Cortez, Reyes‐Quintos et al, ). The same duplication variant was also identified to be associated with otitis‐prone status in US children (Santos‐Cortez et al, ).…”

Genetics and genomic medicine in the Philippines

“…Findings have shown that the A2ML1 genotype is the strongest predictor of otitis media occurrence within this population (Santos‐Cortez et al. ).…”

“…In another related study on otitis media and the indigenous Filipino population, risk factors such as environmental variables, A2ML1 variant carrier status, and middle ear bacteria were analyzed. Findings have shown that the A2ML1 genotype is the strongest predictor of otitis media occurrence within this population (Santos-Cortez et al 2016).…”

Genetic counseling in an indigenous Filipino community with a high prevalence of A2ML1-related otitis media

“…I n t h e P h i l i p p i n e s , a d u p l i c a t i o n v a r i a n t c.2478_2485dupGGCTAAAT (p.Ser829Trpfs*9) within the A2ML1 gene was found to be associated with OM in an indigenous Negrito community (Santos-Cortez et al 2015); this variant confers an increased risk for all types of OM (Santos-Cortez et al 2016b). In this indigenous Filipino population of around 200 individuals from 30 household units, the prevalence of OM was~50% (Santos-Cortez et al 2016b). Historically, this indigenous community has inhabited this region for centuries but they were racially segregated due to their physical features (e.g., dark-colored skin, short stature, flat nose, curly hair).…”