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Combined effect of tumour necrosis factor‐α and interleukin‐13 polymorphisms on bronchial hyperresponsiveness in Korean children with asthma
Author(s) -
Kim HB.,
Kang MJ.,
Lee SY.,
Jin HS.,
Kim JH.,
Kim BS.,
Jang SO.,
Lee YC.,
Sohn MH.,
Kim KE.,
Hong SJ.
Publication year - 2008
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/j.1365-2222.2008.02965.x
Subject(s) - asthma , bronchial hyperresponsiveness , medicine , immunology , odds ratio , allele , methacholine , genotype , immunoglobulin e , case control study , allele frequency , respiratory disease , genetics , biology , gene , antibody , lung
Summary 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 PC 20 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 PC 20 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.