Association of bronchial asthma phenotypes in children with single-nucleotide variants of filaggrin, thymic stromal lymphopoietin and orsomucoid-1-like protein 3 genes
Authors:   Dnipro State Medical University, Ukraine, Dytiatkovskyi V.O. 
Published: December 2023

Bronchial asthma (BA) composes the most severe form of atopic march (AM) in children, which also includes atopic dermatitis (AD),allergic rhinitis and rhino-conjunctivitis (AR/ARC). AM can clinically manifest as mono-organ phenotypes of AD, AR/AR and BA or poly-organ phenotypes of AD+AR/ARC, BA+AR/ARC, AD+AR/ARC+BA. Single nucleotide variants (SNVs) of genes: rs_7927894 of filaggrin (FLG), rs_11466749 of thymic stromal lymphopoietin (TSLP) and rs_7216389 of orsomucoid-1-like protein 3 (ORMDL3) are important factors in the development of AM in children. The aim was to study the role of different variants of rs_7927894 FLG, rs_11466749 TSLP and rs_7216389 ORMDL3 genotypes in the risks of AM - BA, BA+AR/ARC and AD+AR/ARC+BA phenotypes` development. Materials and methods. 121 children of the main group and 105 of the control group aged from 3 to 18 years were involved in the study. Cohorts of the main group: BA - 23 children, BA+AR/ARC - 72 children, AD+AR/ARC+BA - 26 children. The control group consisted of 105 children without AM nosoloies. All children were genotyped by polymerase chain reaction in real time for SNVs C/T, C/C T/T rs_7927894 FLG, A/A, A/G, G/G rs_11466749 TSLP and C/C, C/T, T/T rs_7216389 ORMDL3. For the statistical processing of the obtained results, the methods of variational statistics were applied with the statistical significance threshold at the value of p<0.05, trend to significance - p=0.05-0.1. Results. AD+AR/ARC+BA correlated to BA+AR/ARC: A/G rs_11466749 - reduces the risk, r=0.204, odds ratio (OR)=0.28 (0.08-1.0, p<0.05); T/T rs_7216389 - reduces the risk, r=0.172, OR=0.40 (0.13-1.17, p=0.09). AD+AR/ARC+BA correlated to BA: A/A rs_11466749 – elevates the risk, r=0.259, OR=3.06 (0.9-10.4, p=0.07), A/G rs_11466749 - reduces the risk, r=0.320, OR=0.20 (0.05-0.88, p<0.05). Conclusions. SNV C/T rs_7927894 FLG, A/A rs_11466749 TSLP and T/T rs_7216389 ORMDL3 are associated and elevate the risk of BA+AR/ARC phenotype by 1.87, 1.84 and 3.34 fold, and C/C rs_7216389 ORMDL3 and A/G rs_11466749 TSLP reduce it to 0.42 and 0.56 times. SNV C/T rs_7927894 FLG and A/A rs_11466749 TSLP are associated and increase the risk of developing the full AM AD+AR/ARC+BA phenotype by 3.34 and 3.27fold, and C/C rs_7927894 FLG and A/G rs_11466749 TSLP – are associated and reduce it by 0.45 and 0.15 fold. SNV A/A rs_11466749 TSLP is associated with an elevated risk of developing AD+AR/ARC+BA correlated to BA up to 3.06 fold, and SNV A/G rs_11466749 TSLP is associated and reduces it by 0.20 fold. SNV A/G rs_11466749 TSLP and T/T rs_7216389 ORMDL3 are associated and reduce the risk of AD+AR/ARC+BA phenotype development correlated to BA+AR/ARC by 0.28 and 0.40 fold, respectively. 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 institution mentioned in the work. The informed consent of the parents and the children was obtained for the conducting the study. No conflict of interests was declared by the author.