A repeat polymorphism in interleukin-4 gene is highly associated with specific clinical phenotypes of asthma.

BACKGROUND: IL-4 is a determining factor in immunologic mechanisms to allergy and inflammation. The authors designed a case-controlled study to investigate the potential association of a repeat polymorphism in IL-4 gene with specific clinical phenotypes of asthma. METHODS: The authors used the polymerase chain reaction to characterize the variation of the IL-4 intron 2 region in 145 unrelated Tunisian patients with asthma and 160 healthy control subjects. In order to strengthen the case-controlled study, analysis of IL-4 polymorphism was performed in families of several asthmatic patients. Asthma scores were determined and correlated with this polymorphism. RESULTS: Analysis of IL-4 polymorphism in patients with allergic asthma and in control subjects demonstrated a significant association between the IL-4 A1 allele and asthma. Further evidence of the strong association found between IL-4 intron 2 polymorphism and asthma was provided by the finding that asthma is transmitted in association with the inheritance of the IL-4 A1 marker. When patients were stratified into two groups according to the degree of the severity of asthma, the IL-4 A1 allele was specifically not associated with mild asthma, but highly associated with the moderate and severe forms of the disease. The relative risk (RR) of severe asthma is especially high in patients carrying the A1/A3 genotype (RR = 3.94, p = 0.0001). Conversely, a major decrease in the frequency of the IL-4 A3/A3 genotype was observed in patients with severe asthma, resulting in a significantly negative RR of this clinical phenotype of asthma (RR = 0.165, p = 0.0001). CONCLUSIONS: Tunisian persons carrying the IL-4 A1/A3 genotype may have an increased risk of severe asthma.