IL-5 and thromboxane A2 receptor gene polymorphisms are associated with decreased pulmonary function in Korean children with atopic asthma

Abstract

Asthmatic airways undergo chronic inflammatory cell infiltration by T cells and eosinophils, which results in sustained airway hyperresponsiveness. IL-5 is important for eosinophil-induced airway inflammation and airway hyperresponsiveness. Thromboxane A2 and its receptor, TBXA2R, are involved in constriction of respiratory smooth muscles and may play a role in thickening and remodeling of airways, which contributes to the severity of asthma. The relationship between IL-5 and TBXA2R gene polymorphisms and pulmonary function in children with asthma has rarely been examined. To determine whether IL-5 (T-746C) and TBXA2R (T924C) gene polymorphisms are associated with asthma phenotype and pulmonary function in Korean children with atopic and nonatopic asthma. We conducted an association study between known polymorphisms of IL-5 (T-746C) and TBXA2R (T924C) and asthma phenotype and the parameters of atopy and pulmonary function in atopic and nonatopic Korean children with asthma. The subjects were 240 atopic children with asthma, 70 nonatopic children with asthma, and 106 nonatopic healthy children. Asthma phenotypes and bronchial responsiveness to methacholine were determined by a physician. IL-5 and TBXA2R gene polymorphisms were determined by genotyping by using PCR-RFLP assays. The genotype frequencies of IL-5 and TBXA2R polymorphisms did not differ between healthy controls and atopic or nonatopic children with asthma. A significant association was observed between the IL-5 polymorphism and forced expiratory flow at 25% to 75% of forced vital capacity (FEF 25-75% ; %; P = .002), and between the TBXA2R polymorphism and FEV 1 (%; P = .035) and FEF 25-75% (%; P = .042) in children with atopic asthma, whereas no such association between the polymorphisms and lung function was observed in nonatopic or control children. In atopic children with asthma, we identified a significant gene-gene interaction in that the combination of the IL-5 (T-746C) and TBXA2R (T924C) mutant alleles was shown to be associated with reduced pulmonary function as determined by FEF 25-75% (%) measurement. The current study indicates that IL-5 (T-746C) and TBXA2R (T924C) polymorphisms alone are associated with spirometric markers of asthma severity, whereas they are not associated with presence of asthma per se. In addition, the data suggest that an interaction between IL-5 and TBXA2R genes may contribute to the severity of asthma, especially atopic asthma. These results suggest that IL-5 and TBXA2R genes may be disease-modifying genes in Korean children with atopic asthma.