Genetic susceptibility to chronic otitis media with effusion: Candidate gene single nucleotide polymorphisms

Abstract

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. Study Design 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 single nucleotide polymorphism probes, and genotypes were generated. Quality control across all samples and SNPs reduced the final SNPs used for analysis to 170. Each single nucleotide polymorphism was then analyzed for statistical association with chronic otitis media with effusion. Results Eight single nucleotide polymorphisms from 4 genes had an unadjusted p-value of <0.05 for association with the chronic otitis media with effusion phenotype (TLR4, MUC5B, SMAD2, SMAD4); five of these polymorphisms were in the TLR4 gene. Conclusion While these results need to be replicated in a novel population, the presence of 5 single nucleotide polymorphisms 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.

Otitis media with effusion

“…Recent studies have suggested that children with the condition have a general reduced immunity [39]. This has led to the discovery of potential genes causing susceptibility to the condition [40,41]. It may be possible to use this information in future to identify those at risk and create tailored therapy toward individual patients.…”

Panel 3: Genetics and Precision Medicine of Otitis Media

“…Eight SNPs on 4 genes ( TLR4 , MUC5B , SMAD2 , SMAD4 ) showed a trend toward association ( P BEST_ADJUSTED = .625, rs10116253 on TLR4). 19 …”

Chronic Otitis Media: Microbial Environment During Viral Infection and Genetics of Host Susceptibility

“…We have determined that rs1110060 appears to affect expression of IQGAP1 in adenoids, though a larger population is needed to validate this observation. TGFβ signaling was found to upregulate expression of KIF7 which is important because the TGFβ pathway has been associated with OM in both mouse 71,73 and human studies 95,96,98 . Finally, expression of KIF7 and other HH signaling pathway members decreased after treatment with bacterial LPS.…”

“…Prior studies have found the TGFβ pathway to be important for OM risk in humans 95,96,115,98 and mice 71,72,179 . KIF7 lies within the Sonic hedgehog (SHH) pathway, which has been shown to interact with the TGFβ pathway.…”

“…Suppressor of fused homolog (SUFU), and Patched 1 (PTCH1)), TGFβ pathway member mothers against decapentaplegic homolog 2 (SMAD2), also associated with OM 95,98 , and positive controls (known TGFβ responsiveness genes) PAI1 and SMAD7 were measured as described above. Expression levels of each gene across the treatment time course were compared using a one-way ANOVA in GraphPad Prism.…”