Association Between Antibiotic Exposure, Bronchiolitis, and TLR4 (rs1927911) Polymorphisms in Childhood Asthma

Abstract

PurposeThe complex interplay between environmental and genetic factors plays an important role in the development of asthma. Several studies have yielded conflicting results regarding the 2 asthma-related risk factors: antibiotic usage during infancy and/or a history of bronchiolitis during early life and the development of asthma. In addition to these risk factors, we also explored the effects of Toll-like receptor 4 (TLR4) polymorphism on the development of childhood asthma.MethodsThis cross-sectional study involved 7,389 middle school students who were from 8 areas of Seoul, Korea, and completed the International Study of Asthma and Allergies in Childhood questionnaire. The TLR4 polymorphism rs1927911 was genotyped in 1,395 middle school students from two areas using the TaqMan assay.ResultsBronchiolitis in the first 2 years of life, antibiotic exposure during the first year of life, and parental history of asthma were independent risk factors for the development of asthma. When combined, antibiotic use and a history of bronchiolitis increased the risk of asthma (adjusted odds ratio [aOR]: 4.64, 95% confidence interval [CI]: 3.09-6.97, P value for interaction=0.02). In subjects with CC genotype of TLR4, antibiotic exposure and a history of bronchiolitis during infancy, the risk of asthma was increased, compared to subjects without these risk factors (aOR: 5.72, 95% CI: 1.74-18.87).ConclusionsEarly-life antibiotic exposures and a history of bronchiolitis are risk factors for asthma in young adolescents. Polymorphisms of TLR4 modified the influence of these environmental factors. Reducing antibiotic exposure and preventing bronchiolitis during infancy may prevent the development of asthma, especially in genetically susceptible subjects.

Association of Polymorphisms inToll-Like Receptors 4and9with Autoimmune Thyroid Disease in Korean Pediatric Patients

“…Previous studies have reported that the disease associations of TLR4 with chronic inflammatory disease include atherosclerosis, asthma, and rheumatoid arthritis [ 21 ]. It has been discovered that there is an association of TLR4 rs1927911 SNP with childhood asthma [ 22 ] and disease activity of rheumatoid arthritis [ 23 ] and type 2 diabetes mellitus [ 24 ]. Nicola et al reported that all components of the LPS receptor complex are expressed on thyrocyte, and they also detected that thyroid cells recognize and respond to LPS using Fisher rat thyroid cell line-5 cells [ 8 ].…”

Innate immunity in allergy

“…Mutations in TLR family genes have been investigated using single nucleotide polymorphism (SNP) analysis and meta‐genome‐wide association studies (GWAS). Indeed, SNPs in the TLR4 gene are a risk factor for asthma, indicating that genetic variations of TLR family genes are related to susceptibility to allergic diseases.…”

Association between single nucleotide polymorphisms in TLR4 , TLR2 , TLR9 , VDR , NOS2 and CCL5 genes with acute viral bronchiolitis

“…The SNPs enrolled in our data were selected based on previous published studies (Tal et al, 2004;Löfgren et al, 2010;Goutaki et al, 2014;Murawski et al, 2009;Mailaparambil et al, 2008;Amanatidou et al, 2008;Kresfelder et al, 2011;Janssen et al, 2007;Arruvito et al, 2015;Puthothu et al, 2006;Lee et al, 2015;Fan et al, 2003;Ricciardolo et al, 2004). All SNPs studied are bi-allelic.…”

“…The present study found that death from bronchiolitis is associated with SNP rs4986790 (TLR4), but no association was detected between bronchiolitis severity and SNP rs1927911 (TLR4). SNP rs1927911 (TLR4) was recently associated with an increased risk of asthma development in children with a history of bronchiolitis (Lee et al, 2015), so we are following up our patients to verify any association between bronchiolitis severity, the virus type, genetic polymorphisms, and asthma development. Environmental factors have also been shown to interact with the TLR4 genotype to modulate the RSV infection severity (Caballero et al, 2015).…”