Genotype-associated prognosis of mono-organ and poly-organ atopic marching phenotypes in children

Abstract

Purpose - to research the influence of the single nucleotide variants (SNV) as of thymic stromal lymphopoietin genes (rs11466749 TSLP), orsomucoid-1-like protein 3 (rs7216389 ORMDL3) and human nuclear glucocorticoid receptor type 3 subfamily C member 1 gene (rs 10052957 h-GR/NR3C1) on the risk of developing AM phenotypes «AD», «AD+AR/ARC», «AD+AR/ARC+BA». Materials and methods. 127 children in the main and 105 in the control group aged from 3 to 18 were recruited into the study. All patients underwent the oral cavity mucosa swab, the material of which was subjected genotyping by the means of real-time polymerase chain reaction for SNV variants rs11466749 TSLP, rs7216389 ORMDL3 and rs 10052957 h-GR/NR3C1. For statistical processing the Pearson’s ꭕ2 criteria, Fisher’s exact test, Student’s test was used; the results were considered significant at p<0.05, trending to significance - at p=0.05-0.1. Results. The impact of the studied SNV on the risk of the poly-organ phenotype «AD+AR/ARC» development correlated to the mono-organ ««AD»: G/G rs11466749 TSLP: rs=0.173, OR=5.85 (p=0.08); C/T rs7216389 ORMDL3: rs=0.227, OR=0.36 (p<0.05), T/T rs7216389 ORMDL3: rs=0.227, OR=2.79 (p<0.05); A/G rs 10052957 h-GR/NR3C1: rs=0.215, OR=0.40 (p<0.05), G/G rs 10052957 h-GR/NR3C1: rs=0.263, OR=2.97 (p<0.01). The impact of the studied SNV on the development of the full poly-organ AM phenotype «AD+AR/ARC+BA» correlated to the mono-organ «AD»: A/A rs11466749 TSLP: rs=0.207, OR=2.71 (p=0.09), A/G rs11466749 TSLP: rs=0.310, OR=0.17 (p<0.01), G/G rs11466749 TSLP: rs=0.213, OR=7.43 (p=0.09). Conclusions. Different SNV variants of rs11466749 TSLP, rs7216389 ORMDL3, rs 10052957 h-GR/NR3C1 have both inducing and protective impact on the development of mono-organ and poly-organ AM phenotypes in children. The risk of the mono-organ phenotype «AD» developing into the poly-organ «AD+AR/ARC» is directly associated and significantly increased in carriers of the genotypes T/T rs7216389 ORMDL3 and G/G rs 10052957 h-GR/NR3C1, trending to significance - within G/G rs11466749 TSLP. The bespoke risk is significantly reduced in carriers of C/T rs7216389 ORMDL3 and A/G rs 10052957 h-GR/NR3C1 genotypes. The risk of developing a full poly-organ AM phenotype «AD+AR/ARC+BA» from mono-organ «AD» is significantly reduced in carriers of the A/G rs11466749 TSLP genotype, and is with trend to significance increased within homozygous A/A and G/G rs11466749 TSLP genotypes. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patients and children’s parents was obtained for conducting the studies. No conflict of interests was declared by the author.