Interaction of the TLR4 rs1927911 polymorphism with house dust mite sensitization in allergic rhinitis with its prognosis

Abstract

Background: Sensitization to the house dust mite (HDM) plays important roles in the development of allergic rhinitis (AR). Toll-like receptor 4 (TLR4) is a key initiator of the innate immune system upon exposure to environmental factors. Objective: The present study investigated the independent and interaction effects of HDM sensitization and TLR4 rs1927911 polymorphism on AR and its prognosis in children. Methods: This study included 2,929 children (mean age, 7.8 yrs) from the Children’s HEalth and Environmental Research study (CHEER), a prospective study with a 2-year-interval for 4 years. An ISAAC questionnaire was used with skin prick tests in all subjects. TaqMan genotyping was performed for TLR4 (rs1927911) polymorphism in 1,024 children. Results: HDM sensitization increased risk of current AR (aOR, 2.50; 95%CI, 1.41-4.41; P for interaction = 0.005), current asthma at follow-up (aOR, 4.63; 95%CI, 2.41-8.88; P for interaction < 0.001) and allergic march (aOR, 2.57;95%CI, 1.06-6.22; P for interaction = 0.002) by interacting with genotypes of TLR4 (rs1927911). HDM sensitization increased risk of persistence (aOR, 4.17; 95%CI, 1.77-9.83) and new diagnosis of AR (aOR, 2.48; 95%CI, 1.10-5.61), new sensitization to inhalant allergens (aOR, 10.67; 95%CI, 5.83-19.54), and new development of bronchial hyper-responsiveness (aOR, 5.29; 95%CI, 2.29-12.21) in children with CC genotype of TLR4 rs1927911. Conclusions: HDM sensitization affects AR and its prognosis by interacting with TLR4 rs1957911 polymorphism. The preventive and therapeutic strategies for AR in children need to be targeted in accordance with genetic susceptibility with HDM sensitization.