ABSTRACT
Asthma is the most common chronic childhood disease in developed nations and is a complex has high social and economic costs. Asthma and its associated intermediate phenotypes are under a substantial degree of genetic control. Identifying the genes underlying asthma offers a means of better understanding its pathogenesis.IL-13 is a critical mediator of asthma and allergy. Recent attention has focused on the mechanisms that it uses to induce tissue alterations. IL-13 is a potent stimulator of eosinophilic inflammation, airway fibrosis, mucus metaplasia and airway hyperresponsiveness, Common single-nucleotide polymorphisms in IL-13 are associated with allergic phenotypes in several ethnically diverse populations. In particular, IL13+2044G-A is expected to result in the nonconservative replacement of arginine 130 [R130] with glutamine [Q]. IL-13 variant was able to engage T cells, which depends on enhanced IL-13 mediated Th2 differentiation. Data indicate that natural variation in the coding region of IL-13 may be an important genetic determinant of susceptibility to allergy. Increased serum IgE levels have been found in carriers of IL13+2044A in several populations, raising the possibility that expression of IL-13 R130Q and increased IgE class switching might be mechanistically linked]
Objective: To outline the association of the IL-13 genetic variant R130Q with childhood bronchial asthma and its relation to various clinical and laboratory phenotypes of the disease
Methods: The study was carried out from July 2005 to June 2006. Patients asthmatics enrolled from Allergy and Immunology Unit of Ain Shams University Children's Hospital. All the studied children were subjected to: history taking, careful clinical examination, CBC, serum total IgE by the ELISA technique and detection of IL-13 gene polymorphism [R130Q] by PCR amplification followed by sequencing
Results: The results of the present study showed a significant difference between asthmatic children and controls regarding the frequency of distribution of R130Q genotype which was present in 50% of patients and 15% of controls. No significant differences were observed between patients with IL-13 polymorphism R130Q and those without as regards family history, URTI, food allergy or asthma grading. The serum total IgE as percent of normal was significantly higher in asthmatic patients as compared to controls. While no significant difference was observed between both groups as regard the absolute eisinophilic count[AEC]. Serum total IgE was significantly higher in asthmatics with GA genotype as compared to those with GG genotype. A similar finding was also observed among control group. Finally a significantly higher AEC was observed in controls with GA as compared to GG genotype
Conclusion: the common variant IL-13 gene polymorphism R130Q is associated with the risk of development of pediatric asthma as reflected by the higher laboratory parameters of asthma namely serum total IgE and AEC. Further studies should focus also on other loci on 5q 31-33 such as within the IL-4 and IL-5 genes in the production of the allergic phenotypes and it becomes a necessity to establish the exact genetic profile of our Egyptian asthmatic children. This will help to direct future research in the field of gene therapy of asthma to suit asthmatic children in our country