Combined effect of tumour necrosis factor-α and interleukin-13 polymorphisms on bronchial hyperresponsiveness in Korean children with asthma

Background TNF-alpha 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-alpha - 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-alpha - 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-a 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-alpha - 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-alpha 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-alpha promoter polymorphism and an IL-13 coding region polymorphism in terms of asthma susceptibility and BHR in this population.