Cytokine Polymorphisms Predict the Frequency of Otitis Media As a Complication of Rhinovirus and RSV Infections in Children

Previous studies suggested that the otitis media (OM) complication rate of viral upper respiratory infection (vURI) is conditioned by genes affecting cytokine production. Two hundred and thirty children (114 male; 187 White, 25 Black; aged 1-9.3 years, average=3.6+/-1.6 years) were prospectively followed over the typical cold season for cold-like illness and OM. Nasopharyngeal secretion samples collected during cold-like illness and OM were assayed for upper respiratory viruses and buccal samples were assayed for TNFalpha (-308), IL-10(-1082, -819, -592), IL-6 (-174) and IFN-gamma (+874) polymorphisms. Logistic regression was used to identify genotypes that predict OM coincident with RSV and rhinovirus (RV) infection. Of the 157 children with RV detection (79 male; 132 White, 13 Black, 12 Other; aged 3.6+/-1.5 years), simple logistic regression identified age (B= -0.34, Z= -2.8, P<0.01, OR=0.71), IL-6 (B= -0.76, Z= -3.3, P<0.01, OR=0.47) and IL-10 (B=0.49, Z=2.0, P=0.05, OR=1.6) as significant predictors of OM coincidence. A more complex logistic regression model for RV detection that included selected OM risk factors identified these factors as well as the TNFalpha genotype, OM history, breastfeeding history and daily environment as significant predictors of OM coincidence. Of the 43 children with RSV detection (21 male; 35 White, 5 Black, 3 Other, aged 3.9+/-1.7 years), logistic regression identified IL-10 (B=1.05, Z=2.0, P=0.05, OR=2.9) as a significant predictor of OM coincidence. New OM episodes coincident with evidence of RSV and RV infection were significantly more frequent in children with high production IL-10 phenotypes. The low production IL-6 and high production TNFalpha phenotypes also contributed to OM risk during RV detection. Cytokine polymorphisms may be one of an expectedly large number of genetic factors contributing to the known heritability of OM.