Genetic susceptibility to chronic otitis media with effusion: candidate gene single nucleotide polymorphisms.
OBJECTIVE
The genetic factors leading to a predisposition to otitis media are not well understood. The objective of the current study was to develop a tag-single nucleotide polymorphism (SNP) panel to determine if there is an association between candidate gene polymorphisms and the development of chronic otitis media with effusion.


METHODS
A 1:1 case/control design of 100 cases and 100 controls was used. The study was limited to the chronic otitis media with effusion phenotype to increase the population homogeneity.


METHODS
A panel of 192 tag-SNPs was selected. Saliva for DNA extraction was collected from 100 chronic otitis media with effusion cases and 100 controls. After quality control, 100 case and 79 control samples were available for hybridization. Genomic DNA from each subject was hybridized to the SNP probes, and genotypes were generated. Quality control across all samples and SNPs reduced the final SNPs used for analysis to 170. Each SNP was then analyzed for statistical association with chronic otitis media with effusion.


RESULTS
Eight SNPs from four genes had an unadjusted P value of <.05 for association with the chronic otitis media with effusion phenotype (TLR4, MUC5B, SMAD2, SMAD4); five of these polymorphisms were in the TLR4 gene.


CONCLUSIONS
Even though these results need to be replicated in a novel population, the presence of five SNPs in the TLR4 gene having association with chronic otitis media with effusion in our study population lends evidence for the possible role of this gene in the susceptibility to otitis media.
Department of Otolaryngology-Head and Neck Surgery, Oregon Health and Science University, Portland, Oregon, U.S.A; Oregon Hearing Research Center, Oregon Health and Science University, Portland, Oregon, U.S.A.
Carol J
CJ
MacArthur
Beth
B
Wilmot
Linda
L
Wang
Michael
M
Schuller
Jessyka
J
Lighthall
Dennis
D
Trune
D000293:Adolescent; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D055257:Mucin-5B / Q000235:genetics; D010034:Otitis Media with Effusion / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D051899:Smad2 Protein / Q000235:genetics; D051901:Smad4 Protein / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000235:genetics*
C524578:MUC5B protein, human; D055257:Mucin-5B; C497782:SMAD2 protein, human; C497796:SMAD4 protein, human; D051899:Smad2 Protein; D051901:Smad4 Protein; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4
Otitis media; genetics; innate immune system; single nucleotide polymorphisms