Influence of polymorphic variants rs10455025 of TSLP and rs11811856 of the TNFSF4 gene on the risk of atopic bronchial asthma and allergy in children

Current experimental data indicate the leading role of cytokines in the formation of manifestations of bronchial asthma (BA), thus supporting the so-called anti-cytokine approach to the therapy of this disease. The aim of this study was to evaluate possible association of rs10455025 TSLP gene variant and rs11811856 polymorphism of TNFSF4 gene with the risk of developing BA among children from Kursk population. The study included 999 unrelated individuals, including 526 patients with BA and 473 control persons. These functional gene polymorphisms (SNPs) were genotyped using the MassArray-4 genomic mass spectrometer. We have found that the alleles rs11811856G TNFSF4 and rs10455025C TSLP, as well as the genotypes rs11811856G/G and rs10455025-C/C are associated with an increased risk of developing BA in children. The association of rs11811856 TNFSF4 with an increased risk of developing BA was revealed in both boys and girls. Meawhile, the rs10455025 polymorphism of TSLP gene did not show any associations in the stratified analysis by gender. Upon analysis of gene-environment interactions in general group, a relationship was established with the risk of asthma depending on exposure to tobacco smoke and the place of residence of children. We have found a relationship between the SNP status and the risk of concomitant allergopathology in children with BA, and the influence of the studied polymorphisms on laboratory indices of rhinocytogram and spirometry. The results of this study have shown that the studied SNPs (rs10455025 TSLP and rs11811856 TNFSF4) in children with BA are associated with increased risk of developing food sensitization to banana, rice, duck, and a number of pollen (foxtail, common horsetail, bluegrass, ryegrass, fireweed, ash, barley), and epidermal (human hair) allergens. It has also been found that the studied SNPs reduce the risk of sensitization to house dust, cat hair, rabbit hair, and quinoa pollen. The present study showed that the polymorphic gene variants (rs10455025 TSLP and rs11811856 TNFSF4) are significantly associated with the risk and clinical features of developing BA.

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