RESUMO
The risk of asthma has been increasing in parallel with use of acetaminophen, which is a potential source of oxidative stress. Toll-like receptor 4 (TLR4) plays a critical role not only in innate immunity, but also in mediating reactive oxygen species induced inflammation. Therefore, we investigated associations between acetaminophen usage and TLR4 polymorphism on asthma and bronchial hyperresponsiveness (BHR). The number of 2,428 elementary school children in Seoul and Jeongeup cities was recruited. Subjects who used acetaminophen with a family history of asthma had an increased risk of both asthma diagnosis ever and current asthma. Individuals with CT+TT genotypes at the TLR4 polymorphism, in combination with acetaminophen usage, also demonstrated an increased risk of asthma diagnosis ever (aOR, 2.08; 95% confidence interval [CI], 1.10-3.92). Family history of asthma and acetaminophen usage were risk factors for BHR. Although TLR4 was not an independent risk factor for BHR, individuals with CT+TT genotypes at the TLR4 polymorphism had an increased risk of BHR when combined with acetaminophen usage (aOR, 1.74; 95% CI, 1.03-2.94). In conclusion, acetaminophen usage may be associated with asthma and BHR in genetically susceptible subjects. This effect may be modified by polymorphism at TLR4.
Assuntos
Acetaminofen/efeitos adversos , Asma/genética , Hiper-Reatividade Brônquica/genética , Receptor 4 Toll-Like/genética , Acetaminofen/uso terapêutico , Adolescente , Asma/induzido quimicamente , Asma/epidemiologia , Hiper-Reatividade Brônquica/induzido quimicamente , Hiper-Reatividade Brônquica/epidemiologia , Criança , Estudos Transversais , Eosinófilos/imunologia , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Inflamação/imunologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Polimorfismo de Nucleotídeo Único , Espécies Reativas de Oxigênio/imunologia , Risco , Fatores de Risco , Inquéritos e QuestionáriosAssuntos
Claudina-1/genética , Dermatite Atópica/genética , Fungos/imunologia , Imunoglobulina E/biossíntese , Queratinócitos/imunologia , Pele/imunologia , Animais , Claudina-1/imunologia , Dermatite Atópica/imunologia , Dermatite Atópica/microbiologia , Dermatite Atópica/patologia , Genes Reporter , Humanos , Queratinócitos/efeitos dos fármacos , Queratinócitos/microbiologia , Queratinócitos/patologia , Luciferases/genética , Luciferases/imunologia , Camundongos , Ovalbumina/farmacologia , Patulina/farmacologia , Permeabilidade , Polimorfismo Genético , Cultura Primária de Células , Regiões Promotoras Genéticas , Fatores de Risco , Pele/efeitos dos fármacos , Pele/microbiologia , Pele/patologia , Junções Íntimas/efeitos dos fármacos , Junções Íntimas/imunologia , Junções Íntimas/microbiologia , Junções Íntimas/patologiaRESUMO
PURPOSE: The 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. METHODS: This 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. RESULTS: Bronchiolitis 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). CONCLUSIONS: Early-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.