Abstract
Asthma is a complex genetic disorder that is associated with both genetic and environmental factors. The aim of study was to investigate the combined effect of toll-like receptor 4 (TLR4), cluster of differentiation 14 (CD14), and interleukin-13 (IL-13) polymorphisms and bronchiolitis in the development of childhood asthma. A modified International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire was used to survey 1,341 elementary school children and 919 nursery children in Seoul, Korea. TLR4 (rs1927911), CD14 (rs2569190), and IL-13 (rs20541) polymorphisms were genotyped by the TaqMan assay. In elementary school and nursery children, parental history of asthma (adjusted odds ratio [aOR] 2.56 [95% CI 1.16-5.63], aOR 3.60 [95% CI 1.66-7.76], respectively), and past history of bronchiolitis (aOR 3.11 [95% CI 1.84-5.24], aOR 3.94 [95% CI 2.27-6.84], respectively) were independent risk factors for asthma diagnosis. When compared to children with each CC of TLR4 polymorphism or TT of CD14 polymorphism or GG of IL13 polymorphism and no past history of bronchiolitis, children with CT or TT of TLR4 polymorphism and past history of bronchiolitis had 4.23 and 5.34 times higher risk to develop asthma, respectively; children with TT of CD14 polymorphism and past history of bronchiolitis had 3.57 and 7.22 times higher risk for asthma, respectively; children with GA or AA of IL-13 polymorphism and past history of bronchiolitis had 3.21 and 4.13 times higher risk for asthma, respectively. Family history of asthma or allergic rhinitis and past history of bronchiolitis could be independent risk factors for the development of childhood asthma. The relationship between asthma and bronchiolitis is modified by the TLR4, CD14, and IL-13 polymorphisms in Korean children.
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