The Association of Genetic Variants in Toll-like Receptor 2 Subfamily With Allergy and Asthma After Hospitalization for Bronchiolitis in Infancy

Background: Toll-like receptors (TLRs) are a pivotal part of the innate immunity system. Variations in TLR genes have been connected to autoimmune conditions, such as allergy and asthma. The TLR2 subfamily comprises TLR1, TLR2, TLR6 and TLR 10. We hypothesized that polymorphism of the TLR2 subfamily may be associated with prevalence of post-bronchiolitic asthma and/or atopy. Methods: TLR1rs5743618, TLR2rs5743708 and TLR6rs5743810 single nucleotide polymorphisms of 133 children who had been hospitalized for bronchiolitis at <6 months of age were analyzed. Doctor-diagnosed asthma and atopy as well as their occurrence during the first 6 years of life were evaluated during a follow-up visit. Results: At the mean age of 6.4 years, asthma was present in 17 (13%) patients, there was asthma diagnosis during the first 6 years of life in 39 (29%) and current doctor-diagnosed allergic rhinitis in 57 (43%) patients. Twenty-four (24%) children with G/G genotype in TLR1 rs5743618 were diagnosed to have asthma between 1 and 6 years of age (vs. 13 (38%) of those with G/T or T/T genotypes; P = 0.04). In addition, 11/60 (18%) children with TLR6 rs5743810 C/T versus 36/73 (49%) children of other genotypes had atopic eczema at follow up. Only 2 children (8%) with wild genotype in all investigated single nucleotide polymorphisms had asthma during the first 6 years of life (vs. 30% in those with variant genotype of TLR1, TLR2 and/or TLR6). Conclusion: In this study, we demonstrated that TLR1 rs5743618 was associated with asthma and atopic eczema during the first 6 years of life after early bronchiolitis. In addition, TLR6 rs5743810 was associated with present atopy at preschool age.