title: Genetic and Environmental Determinants of Otitis Media in an Indigenous Filipino Population.
abstract: To identify genetic and environmental risk factors for otitis media in an indigenous Filipino population.
  
  
  
  Cross-sectional study.
  
  
  
  Indigenous Filipino community.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Center for Statistical Genetics, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA santosco@bcm.edu.
authors.forename: Regie Lyn P
authors.initials: RL
authors.lastname: Santos-Cortez
authors.affiliation: Philippine National Ear Institute, University of the Philippines Manila-National Institutes of Health, Manila, Philippines.|Department of Otorhinolaryngology, University of the Philippines College of Medicine-Philippine General Hospital, Manila, Philippines.
authors.forename: Ma Rina T
authors.initials: MR
authors.lastname: Reyes-Quintos
authors.affiliation: Philippine National Ear Institute, University of the Philippines Manila-National Institutes of Health, Manila, Philippines.|Department of Otorhinolaryngology, University of the Philippines College of Medicine-Philippine General Hospital, Manila, Philippines.
authors.forename: Ma Leah C
authors.initials: ML
authors.lastname: Tantoco
authors.affiliation: Center for Statistical Genetics, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Izoduwa
authors.initials: I
authors.lastname: Abbe
authors.affiliation: Philippine National Ear Institute, University of the Philippines Manila-National Institutes of Health, Manila, Philippines.|Department of Otorhinolaryngology, University of the Philippines College of Medicine-Philippine General Hospital, Manila, Philippines.
authors.forename: Erasmo Gonzalo D V
authors.initials: EG
authors.lastname: Llanes
authors.affiliation: Alkek Center for Metagenomics and Microbiome Research (CMMR), Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Nadim J
authors.initials: NJ
authors.lastname: Ajami
authors.affiliation: Alkek Center for Metagenomics and Microbiome Research (CMMR), Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Diane S
authors.initials: DS
authors.lastname: Hutchinson
authors.affiliation: Alkek Center for Metagenomics and Microbiome Research (CMMR), Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Petrosino
authors.affiliation: Institute of Human Genetics, University of the Philippines Manila-National Institutes of Health, Manila, Philippines.|Department of Pediatrics, University of the Philippines College of Medicine-Philippine General Hospital, Manila, Philippines.|Philippine Genome Center, University of the Philippines Diliman, Quezon City, Philippines.
authors.forename: Carmencita D
authors.initials: CD
authors.lastname: Padilla
authors.affiliation: Philippine National Ear Institute, University of the Philippines Manila-National Institutes of Health, Manila, Philippines.|Department of Otorhinolaryngology, University of the Philippines College of Medicine-Philippine General Hospital, Manila, Philippines.
authors.forename: Romeo L
authors.initials: RL
authors.lastname: Villarta
authors.affiliation: Philippine National Ear Institute, University of the Philippines Manila-National Institutes of Health, Manila, Philippines.|Department of Otorhinolaryngology, University of the Philippines College of Medicine-Philippine General Hospital, Manila, Philippines.
authors.forename: Teresa Luisa
authors.initials: TL
authors.lastname: Gloria-Cruz
authors.affiliation: Philippine National Ear Institute, University of the Philippines Manila-National Institutes of Health, Manila, Philippines.|Department of Otorhinolaryngology, University of the Philippines College of Medicine-Philippine General Hospital, Manila, Philippines.
authors.forename: Abner L
authors.initials: AL
authors.lastname: Chan
authors.affiliation: Institute of Human Genetics, University of the Philippines Manila-National Institutes of Health, Manila, Philippines.|Department of Pediatrics, University of the Philippines College of Medicine-Philippine General Hospital, Manila, Philippines.|Philippine Genome Center, University of the Philippines Diliman, Quezon City, Philippines.
authors.forename: Eva Maria
authors.initials: EM
authors.lastname: Cutiongco-de la Paz
authors.affiliation: Philippine National Ear Institute, University of the Philippines Manila-National Institutes of Health, Manila, Philippines.|Department of Otorhinolaryngology, University of the Philippines College of Medicine-Philippine General Hospital, Manila, Philippines.
authors.forename: Charlotte M
authors.initials: CM
authors.lastname: Chiong
authors.affiliation: Center for Statistical Genetics, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Leal
authors.affiliation: Philippine National Ear Institute, University of the Philippines Manila-National Institutes of Health, Manila, Philippines.|Department of Otorhinolaryngology, University of the Philippines College of Medicine-Philippine General Hospital, Manila, Philippines.
authors.forename: Generoso T
authors.initials: GT
authors.lastname: Abes
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D004781:Environmental Exposure / Q000009:adverse effects*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D064307:Microbiota; D010033:Otitis Media / Q000453:epidemiology* / Q000235:genetics* / Q000382:microbiology; D038781:Otoscopy; D010679:Philippines / Q000453:epidemiology; D015995:Prevalence; D012307:Risk Factors; D000511:alpha-Macroglobulins / Q000235:genetics*
chemical_list: C510358:A2ML1 protein, human; D000511:alpha-Macroglobulins
keywords: A2ML1; Philippines; indigenous population; microbiome; middle ear; otitis media