Association between cytokine gene polymorphisms and risk for upper respiratory tract infection and acute otitis media

Background. We previously reported an association between tumor necrosis factor α (TNFα) ^-308and interleukin (IL)-6 ^-174 polymorphisms and otitis susceptibility by history. Acute otitis media occurs most commonly as a complication of upper respiratory tract infection (URI); it is not clear why some children develop acute otitis media after URI and others do not. Our objective was to prospectively evaluate the association of TNFα ^-308and IL-6 ^-174 polymorphisms with URI and with acute otitis media development after URI. Methods. Children aged 6-35 months were prospectively followed for occurrences of URI and acute otitis media. Blood or buccal mucosa samples were collected for DNA extraction to determine cytokine genotypes. Active and passive surveillance was used to capture all URI episodes during the 1-year follow-up period in order to study the rate of acute otitis media following URI. Data were analyzed using SAS software (SAS Institute) and general estimating equations modeling. Results. Two hundred forty-two children were followed over 2689 patient-months and had DNA genotyped; 1235 URI episodes occurred, and 392 (32%) were complicated by acute otitis media. Children who had IL-6 ^-174 polymorphism had a higher susceptibility to URI during the study period (incidence density ratio, 1.24) and were more likely to meet established otitis susceptibility criteria (P < .01). Presence of TNFα ^-308 polymorphism was associated with increased risk for acute otitis media after an episode of URI (odds ratio, 1.43). Conclusions. TNFα ^-308 and IL-6 ^-174 genotypes are associated with increased risk for symptomatic URI and acute otitis media following URI. Future studies may be designed to carefully look at the interaction of these genetic polymorphisms with modifiable environmental risk factors.