title: Evaluation of 15 functional candidate genes for association with chronic otitis media with effusion and/or recurrent otitis media (COME/ROM).
abstract: DNA sequence variants in genes involved in the innate immune response and secondary response to infection may confer susceptibility to chronic otitis media with effusion and/or recurrent otitis media (COME/ROM). We evaluated single nucleotide polymorphisms (SNPs) in 15 functional candidate genes. A total of 99 SNPs were successfully genotyped on the Sequenom platform in 142 families (618 subjects) from the Minnesota COME/ROM Family Study. Data were analyzed for association with COME/ROM using the Generalized Disequilibrium Test (GDT). Sex and age at exam were adjusted as covariates, relatedness was accounted for, and genotype differences from all phenotypically discordant relative pairs were utilized to measure the evidence of association between COME/ROM and each SNP. SNP rs2735733 in the region of the mucin 5, subtypes A/C gene (MUC5AC) exhibited nominal evidence for association with COME/ROM (P = 0.002). Two additional SNPs from this region had P values<0.05. Other variants exhibiting associations with COME/ROM at P<0.05 included the SCN1B SNP rs8100085 (P = 0.013), SFTPD SNP rs1051246 (P = 0.039) and TLR4 SNP rs2770146 (P = 0.038). However, none of these associations replicated in an independent sample of COME/ROM families. The candidate gene variants examined do not appear to make a major contribution to COME/ROM susceptibility, despite a priori evidence from functional or animal model studies for a role in COME/ROM pathology.
authors.affiliation: Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia, United States of America. msale@virginia.edu
authors.forename: Michèle M
authors.initials: MM
authors.lastname: Sale
authors.forename: Wei-Min
authors.initials: WM
authors.lastname: Chen
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Weeks
authors.forename: Josyf C
authors.initials: JC
authors.lastname: Mychaleckyj
authors.forename: Xuanlin
authors.initials: X
authors.lastname: Hou
authors.forename: Miranda
authors.initials: M
authors.lastname: Marion
authors.forename: Fernando
authors.initials: F
authors.lastname: Segade
authors.forename: Margaretha L
authors.initials: ML
authors.lastname: Casselbrant
authors.forename: Ellen M
authors.initials: EM
authors.lastname: Mandel
authors.forename: Robert E
authors.initials: RE
authors.lastname: Ferrell
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Rich
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Daly
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D002648:Child; D002908:Chronic Disease; D005192:Family Health; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D055271:Mucin 5AC / Q000235:genetics; D010033:Otitis Media / Q000235:genetics* / Q000473:pathology; D010034:Otitis Media with Effusion / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D012008:Recurrence; D015222:Sodium Channels / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000235:genetics; D062547:Voltage-Gated Sodium Channel beta-1 Subunit; D055815:Young Adult
chemical_list: C524678:MUC5AC protein, human; D055271:Mucin 5AC; C470379:SCN1B protein, human; D015222:Sodium Channels; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D062547:Voltage-Gated Sodium Channel beta-1 Subunit