Interactions Between Innate Immunity Genes and Early-Life Risk Factors in Allergic Rhinitis

PURPOSE: Allergic rhinitis (AR) is a common chronic disease. Many factors could affect the development of AR. We investigated early-life factors, such as delivery mode, feeding method, and use of antibiotics during infancy, which could affect the development of AR. In addition, how interactions between these factors and innate gene polymorphisms influence the development of AR was investigated. METHODS: A cross-sectional study of 1,828 children aged 9-12 years was conducted. Three early-life factors and AR were assessed by a questionnaire. Skin prick tests were done. Polymorphisms of TLR4 (rs1927911) and CD14 (rs2569190) were genotyped. RESULTS: Use of antibiotics during infancy increased the risk of AR (aOR [95% CI] 1.511 [1.222-2.037]) and atopic AR (aOR [95% CI], 1.565 [1.078-2.272]). There were synergistic interactions between caesarean delivery, formula feeding, and use of antibiotics in the rate of atopic AR (aOR [95% CI], 3.038 [1.256-7.347]). Additional analyses revealed that the risk for the development of AR or atopic AR subjects with the TLR4 CC genotype were highest when all the 3 early-life factors were present (aOR [95% CI], 5.127 [1.265-20.780] for AR; 6.078 [1.499-24.649] for atopic AR). In addition, the risk for the development of AR or atopic AR in subjects with the CD14 TT genotype were highest when all the 3 early-life factors were present (aOR [95% CI], 5.960 [1.421-15.002] for AR; 6.714 [1.440-31.312] for atopic AR). CONCLUSIONS: Delivery mode, feeding method, and use of antibiotics during infancy appeared to have synergistic interactions in the development of AR. Gene-environment interactions between polymorphism of innate genes and early- life risk factors might affect the development of AR.