Association Analysis of Tyrosine Kinase FYN Gene Polymorphisms in Asthmatic Children

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Abstract
Background: FYN is nonreceptor tyrosine kinase that represents the earliest detectable signaling response after antigen-activated inflammatory cells. Studies in animal models of allergic asthma have shown that inhibitors of tyrosine kinases exert an anti-inflammatory effect. In the FYN gene, several polymorphisms have been described. There have, however, been no studies analyzing the impact of FYN gene polymorphisms on the course and severity of asthma. The aim of this study was to analyze the possible relationship between three polymorphisms (–93A/G, Intron10+37C/T and Ex12+894T/G) in the FYN gene and asthma. Methods: We analyzed 120 pediatric asthmatic patients aged from 6 to 18 years. The diagnosis of allergic asthma was based on clinical manifestation, lung function test and positive skin prick tests and/or an increased IgE level. The control group consisted of 187 healthy subjects. The polymorphisms were genotyped with use of the PCR-RFLP method. Results: We observed an association of the –93A/G polymorphism and the presence of asthma (p = 0.014 for genotypes and p = 0.019 for alleles) and in the subgroup of 55 patients with severe asthma (p = 0.042 for genotypes and p = 0.021 for alleles). We also found an association of the Ex12+894T/G polymorphism in the whole group analyzed (p = 0.067 for genotypes and p = 0.024 for alleles), but not in the subgroup with severe asthma. For the Intron10+37T/C polymorphism, we did not find a significant difference between the whole group of asthmatic patients and the control group nor between the subgroup with severe asthma and the control group. In the linkage disequilibrium analysis, we observed a modest linkage between –93A/G and Intron10+37T/C polymorphisms (lod = 18.7, D’ = 0.62, 95% CI: 0.51–0.71, r2 = 0.29); however, it was not strong enough to generate any haplotypes. Conclusions: The results may suggest a relationship between the FYN polymorphisms and allergic asthma.