Evaluation of 15 functional candidate genes for association with chronic otitis media with effusion and/or recurrent otitis media (COME/ROM)

• Published in: PloS one Vol. 6; no. 8; p. e22297
• Main Authors: Sale, Michèle M, Chen, Wei-Min, Weeks, Daniel E, Mychaleckyj, Josyf C, Hou, Xuanlin, Marion, Miranda, Segade, Fernando, Casselbrant, Margaretha L, Mandel, Ellen M, Ferrell, Robert E, Rich, Stephen S, Daly, Kathleen A
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 16.08.2011; Public Library of Science (PLoS)
• Subjects: Adolescent; Adult; Alleles; Analysis; Biology; C gene; Child; Children & youth; Chronic Disease; Chronic infection; Data processing; Deoxyribonucleic acid; Diseases; DNA; Ear diseases; Effusion; Families & family life; Family Health; Family studies; Female; Gene expression; Gene Frequency; Genes; Genetic aspects; Genetic Predisposition to Disease - genetics; Genetics; Genomics; Genotype; Genotypes; Glycoproteins; Haemophilus influenzae; Health sciences; Humans; Immune response; Immune system; Influenza; Innate immunity; Linkage Disequilibrium; Male; Medical records; Medicine; Middle Aged; Mucin; Mucin 5AC - genetics; Mucins; Mutation; Nucleotide sequence; Otitis media; Otitis Media - genetics; Otitis Media - pathology; Otitis media with effusion; Otitis Media with Effusion - genetics; Otitis Media with Effusion - pathology; Otolaryngology; Pediatrics; Polymorphism, Single Nucleotide; Proteins; Public health; Recurrence; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Sodium Channels - genetics; Surfactants; TLR4 protein; Toll-Like Receptor 4 - genetics; Toll-like receptors; Vaccines; Voltage-Gated Sodium Channel beta-1 Subunit; Young Adult; Pittsburgh Pennsylvania; United States > US; Virginia; Pennsylvania
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0022297

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.