Combined effect of tumour necrosis factor-α and interleukin-13 polymorphisms on bronchial hyperresponsiveness in Korean children with asthma
Article first published online: 13 MAR 2008
© 2008 The Authors
Clinical & Experimental Allergy
Volume 38, Issue 5, pages 774–780, May 2008
How to Cite
Kim, H.-B., Kang, M.-J., Lee, S.-Y., Jin, H.-S., Kim, J.-H., Kim, B.-S., Jang, S.-O., Lee, Y.-C., Sohn, M.-H., Kim, K.-E. and Hong, S.-J. (2008), Combined effect of tumour necrosis factor-α and interleukin-13 polymorphisms on bronchial hyperresponsiveness in Korean children with asthma. Clinical & Experimental Allergy, 38: 774–780. doi: 10.1111/j.1365-2222.2008.02965.x
- Issue published online: 13 MAR 2008
- Article first published online: 13 MAR 2008
- Submitted 7 June 2007; revised 28 November 2007, accepted 10 January 2008
- bronchial hyperresponsiveness;
- combined effect;
Background TNF-α and IL-13, two pivotal pro-inflammatory cytokines, are increased in asthmatic airways and may be linked to asthma susceptibility and/or bronchial hyperresponsiveness (BHR).
Objective We investigated the association between the TNF-α−308G/A polymorphism and asthma susceptibility or asthma-related phenotypes in Korean children with asthma, and tested for a combined effect with IL-13 polymorphisms.
Methods Asthmatic children (n=719) and non-atopic healthy control children (n=243) were evaluated for asthma phenotypes including total serum IgE and BHR to methacholine. Genotypes were determined by PCR-restriction fragment length polymorphism analysis.
Results The allele frequency of TNF-α−308A in asthmatics (14.1%) was higher than that in control children [8.7%, odds ratio (OR) 1.72, 95% confidence interval (CI) 1.05–2.82]. Significantly lower PC20 values were found in asthmatic children carrying one or two copies of the TNF-α risk allele (−308A) vs. those homozygous for the common allele (P=0.026). Combined analysis revealed that atopic asthmatic children co-inherited the risk alleles of TNF-α−308G/A and IL-13 +2044G/A more frequently than control children (aOR 1.91, 95% CI 1.00–3.65), and asthmatic children co-inheriting both risk alleles had significantly lower PC20 values vs. asthmatic children homozygous for the common alleles (P=0.024).
Conclusion The TNF-α promoter polymorphism (−308G/A) may be associated with asthma susceptibility and BHR in Korean children with asthma. In addition, there appears to be a synergistic effect between the TNF-α promoter polymorphism and an IL-13 coding region polymorphism in terms of asthma susceptibility and BHR in this population.