TNF-α (−308 G/A) and CD14 (−159T/C) polymorphisms in the bronchial responsiveness of Korean children with asthma

BackgroundTNF-α is a pivotal proinflammatory cytokine increased in asthmatic airways. The TNF-α gene family might be linked to asthma or bronchial hyperresponsiveness (BHR), and TNF-α production might be modulated by CD14+ cells.ObjectiveWe investigated the association between asthma susceptibility or asthma-related phenotypes and TNF-α (−308G/A) polymorphism and examined the combined effect with CD14 (−159T/C) polymorphism in Korean children.MethodsAsthmatic (n = 788) and control (n = 153) children were evaluated for asthma phenotypes. Genotypes were determined by using the single-base extension method and PCR–restriction fragment length polymorphism.ResultsThere was no difference between asthmatic children and control subjects in terms of the allele frequencies of TNF-α (−308G/A) and CD14 (−159T/C). Significantly lower PC20 values were seen in asthmatic (P = .016) children with the TNF-α risk allele (−308A). Higher frequencies of 1 or 2 copies of the risk allele were found in asthmatic children with moderate-to-severe BHR to methacholine and exercise compared with control children (adjusted odds ratio of 2.57 [95% CI, 1.30-5.08] and adjusted odds ratio of 2.04 [95% CI 0.99-4.20], respectively). In addition, asthmatic children with risk alleles at both loci had significantly greater BHR than those homozygous for the common alleles (P = .018).ConclusionThe TNF-α promoter polymorphism (−308G/A) might be associated with severe BHR in Korean children with asthma. In addition, these children show a synergistic effect between the TNF-α promoter (−308A) and CD14 promoter (−159C) polymorphisms in terms of BHR.Clinical implicationsThe TNF-α polymorphism might be a disease-modifying gene in asthma and modulated by the CD14 gene.