A Repeat Polymorphism in Interleukin–4 Gene Is Highly Associated with Specific Clinical Phenotypes of Asthma

Abstract

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.

Association of <i>IL4</i> Gene Polymorphisms with Asthma in North Indians

“…Allele 54 (designated A1) has also been shown to be associated with asthma in a Tunisian population [32]. Further, in our study, a highly significant difference was obtained in the overall genotype distribution in the two groups using the Fisher-Freeman-Halton test (Fisher statistic = 46.65, p = 0.0009).…”

Interleukin 3 (IL3) polymorphisms associated with decreased risk of asthma and atopy

“…They act on target cells to cause a wide array of cellular functions including activation, proliferation, immunomodulation, and release of other cytokines or mediators. Several researchers have reported the functions of cytokines in asthma as well as association with their polymorphisms with asthma (Chouchane et al 1999;Chung and Barnes 1999;Hobbs et al 1998;Walley and Cookson 1996;Zhang et al 2002).…”

“…Several interleukins have been reported to be involved in asthma through the pathological and immunological pathways as lymphokines, proinflammatory cytokines, and anti-inflammatory cytokines (Bagley et al 1997;Chouchane et al 1999;Chung and Barnes 1999;Karjalainen et al 2003a;Renauld 2001). The IL1 gene complex is involved in the regulation of IgEmediated atopic reactions and eosinophil accumulation in vivo (Chung and Barnes 1999).…”

Association of IL4R gene polymorphisms with asthma in Chinese populations

“…Although positive associations of polymorphisms within cytokine genes on 5q31 with asthma have been reported [Chouchane et al, 1999;Chung and Barnes, 1999;Hobbs et al, 1998;Walley and Cookson,1996;Zhang et al, 2002], we failed to observe any association with susceptibility to asthma for polymorphisms of IL13, IL4, IL5, IL3, IL9, CD14, and IL12B. Several factors could provide plausible explanations, e.g., (1) possible genetic differences between different ethnic groups, (2) small size of this study [especially normal controls (n=114)], and (3) different study designs and possible biases in recruiting case and controls among studies.…”