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  • Title: TNF-alpha (-308 G/A) and CD14 (-159T/C) polymorphisms in the bronchial responsiveness of Korean children with asthma.
    Author: Hong SJ, Kim HB, Kang MJ, Lee SY, Kim JH, Kim BS, Jang SO, Shin HD, Park CS.
    Journal: J Allergy Clin Immunol; 2007 Feb; 119(2):398-404. PubMed ID: 17196641.
    Abstract:
    BACKGROUND: TNF-alpha is a pivotal proinflammatory cytokine increased in asthmatic airways. The TNF-alpha gene family might be linked to asthma or bronchial hyperresponsiveness (BHR), and TNF-alpha production might be modulated by CD14(+) cells. OBJECTIVE: We investigated the association between asthma susceptibility or asthma-related phenotypes and TNF-alpha (-308G/A) polymorphism and examined the combined effect with CD14 (-159T/C) polymorphism in Korean children. METHODS: Asthmatic (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. RESULTS: There was no difference between asthmatic children and control subjects in terms of the allele frequencies of TNF-alpha (-308G/A) and CD14 (-159T/C). Significantly lower PC(20) values were seen in asthmatic (P = .016) children with the TNF-alpha 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). CONCLUSION: The TNF-alpha 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-alpha promoter (-308A) and CD14 promoter (-159C) polymorphisms in terms of BHR. CLINICAL IMPLICATIONS: The TNF-alpha polymorphism might be a disease-modifying gene in asthma and modulated by the CD14 gene.
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