Korean J Asthma Allergy Clin Immunol.
2007 Jun;27(2):98-104.
Gene-Gene Interaction between TNF-alpha -308G/A and IL-13 +2044G/A Polymorphisms with Bronchial Hyperresponsiveness in Korean Children
Abstract
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BACKGROUND: Asthma is the most common chronic disease in children. Tumor necrosis factor (TNF)-alpha is a pivotal proInflammatory cytokine increased in the asthmatic airways. Also, interleukin (IL)-13 is a pivotal immunoregulatory cytokine in asthma pathogenesis.
OBJECTIVE
We assumed that there might be a synergistic effect between TNF-alpha and IL-13. We analyzed the genotypes of TNF-alpha and IL-13 polymorphisms in asthmatic patients and control groups, and investigated the association of asthma-related phenotypes with them.
METHOD: We enrolled 719 asthmatic and 172 control children. Evaluated asthma phenotypes included pulmonary function test, and bronchial hyperresponsiveness (BHR) to methacholine and exercise. We analyzed the genotypes of TNF-alpha -308G/A and IL-13 +2044G/A polymorphism by using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.
RESULT: TNF-alpha polymorphism was associated with BHR to methacholine (P=0.026). Gene-gene interactions between TNF-alpha and IL-13 polymorphisms with heterozygote and homozygote of variant genotypes were associated with BHR to methacholine in asthma (P=0.008) and exercise-induced asthma (P=0.005) but were not associated with maximum % fall in FEV1 compared to those with homozygotes of common genotypes.
CONCLUSION
TNF-alpha polymorphism was associated with BHR to methacholine. Gene-gene interactions between TNF-alpha and IL-13 polymorphisms were associated with BHR to methacholine. Therefore, TNF-alpha and IL-13 polymorphisms may show a synergistic effect in terms of BHR.