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Association of Q551R polymorphism in the interleukin 4 receptor gene with nonatopic asthma in Slovenian children

BACKGROUND: Asthma is one of the most common chronic diseases of childhood and results from the interaction of several genes and environmental influences. Interleukin 4 (IL4) and its receptor IL4R have a central role in the regulation of immunoglobulin E (IgE) production and thereby in the induction and maintenance of allergy and asthma. The single nucleotide polymorphisms (SNPs) Q551R in the IL4RA gene and C-33T in the IL4 gene probably influence IL4/IL4R pathway signaling; however, findings in association studies exploring the role of these two genes in asthma pathogenesis are contradictory. We have studied the association of IL4RA Q551R and IL4 C-33T SNPs with asthma, asthma phenotypes, and clinical and laboratory parameters. METHODS: The study group comprised 106 children aged between 5 and 18 years with mild or moderate persistent asthma: 78 children were atopic and 28 had nonatopic asthma. The children underwent allergy and spirometry tests, a bronchoprovocation test with methacholine, measurement of exhaled nitric oxide in expired air and genotyping for IL4RA Q551R and IL4 C-33T SNPs. Genotype data from 89 nonatopic nonasthmatics served as a control group. RESULTS: The frequency of the IL4RA Arg551 allele in the children with nonatopic asthma was 7.1%, significantly lower than 21.9% in the control group (P = 0.01, OR: 0.33, 95% CI: 0.12–0.87). Allelic and genotype frequencies in IL4 C-33T polymorphism in the asthma group and the control group were not significantly different. The mean value of total IgE in asthmatics with the IL4-33C allele was 556.0 IU/l, significantly higher than 371.6 IU/l in those with the T allele (P = 0.02). In an interaction study we did not find significant differences in the frequencies of any combinations of IL4RA Q551R and IL4 C-33T alleles between asthmatics and controls. CONCLUSIONS: The IL4RA Q551R SNP is associated with nonatopic asthma in Slovenian children. This finding contributes to knowledge about an important asthma phenotype pathogenesis and could serve in future research into new strategies for asthma management.

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