The role of mutations in metalloproteinases and the epithelial growth factor receptor genes in the pathogenesis of children bronchial asthma

The pathogenesis of bronchial asthma (BA) is based on chronic allergic inflammation of bronchi, which affects not only microcirculation disorders, activation of lipid peroxidation, but also tissue remodeling. Matrix metalloproteinases (MMP) and epithelial growth factor (EGF) play a significant role in bronchial remodelling processes. This paper attempts to investigate the effect of gene mutations ММР and EGFR on the development of BA as well as evaluate the role of intergenic interaction. Methods. Polymorphic variants were studied in BA patients and control group patients by allelspecific polymerase chain reaction (using SNP-express reagent kits). 2073A>T gene EGFR, 320A>C gene MMP20, 837Т>C gene MMP20 и -8202A>G gene MMP9. Results. The analysis of the genetic study results showed statistically significant differences in the frequency of alleles and genotypes in polymorphism. 2073A>T gene EGFR among BA patients and control group children (p < 0.05). Significantly increased allel frequency is registered. 2073T gene EGFR in the group of BA patients (82.5%) compared to the control group (55.8%) (p = 0.003). In the study of genes polymorphisms of matrix metalloproteinases no statistically significant differences were revealed. However, the analysis of intergenic interaction shows that polymorphisms -8202A>G gene MMP9 and 2073A>T gene EGFR have a synergistic effect on each other, increasing the risk of developing BA in children. Conclusion. According to the results of studies it was found that the risk of BA development is significantly increased in homozygotes on T-allel polymorphic variant 2073A>T gene EGFR, with the frequency of occurrence of genotypes and alleles of this polymorphism statistically significantly different from the control group (p < 0.05).

bronchial asthma, genetics, polymorphism, matrix metalloproteinases, epidermal growth factor receptor

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