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

Abstract

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 PC(20) values were found in asthmatic children carrying one or two copies of the TNF-alpha 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 PC(20) 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.