Role of single nucleotide variants of thymic stromal lymphopoietin in the mono- and polyorganic lesions within atopic disorders in children
Authors:   Dnipro State Medical University, Ukraine, Dytiatkovskyi V.O. 
Published: March 2022

Atopic diseases (AtD) in children — atoic dermamatitis (AD), allergic rhinitis / rhinoconjunctivits (AR/ARC), bronchial asthma (BA) — remain an actual problem in modern pediatrics. Thymic stromal lymphopoietin (TSLP) is one of the key agents involved in the development of allergic inflammation in the barrier organs — the skin and mucous membranes of the airways. The role of single nucleotide variants (SNVs) of the TSLP gene in the development of monoorganic or polyorganic lesions within AD in children has been insufficiently studied and needs to be elucidated. Purpose — to determine the role of SNV rs11466749 of TSLP gene in the risk of developing mono- and polyorganic phenotypes of AtD in children (AD, AR/ARC and/or asthma). Materials and methods. The study recruited 293 children into the main and 105 — into control groups aged 3 to 18 years. Patients of the main group had been clinically diagnosed with of AD, AR/ARC and BA isolated or in different combinations. Patients in the control group were clinically excluded the diagnosis of AD and diagnosed with diseases of the digestive system (chronic gastritis, chronic duodenitis, peptic ulcer disease, functional disorders of the biliary system). For genotyping of the variants A/A, A/G, G/G SNV rs11466749 of the TSLP gene, buccal swab of the oral mucosa was performed in patients of the main and control groups. Cluster analysis was used, for which all patients of the main group were divided into 6 clusters: with monoorganic lesions: № 1 — AD (58 patients), № 2 — AR/ARC (71 patient), № 3 — BA (26 patients); with polyorganic lesions: № 4 — AD+AR/ARC (43 patients); № 5 — BA+AR/ARC (23 patients); № 6 — AD+AR/ARC+BA (72 patients). Comparative analysis between clusters was performed for the genotype variants A/A, A/G, G/G SNV rs11466749 TSLP gene. The criterion of statistical significance was determined as p<0.05. Results. The A/A genotype SNV rs11466749 of TSLP gene is the most common variant in patients with AtD and significantly increases the risk of their development by 1.61 fold. Variant A/G SNV rs11466749 of TSLP gene is antagonistic to A / A and is significantly more common in patients without AtD and decreases the risk of their development by 1.69 times. The A/A genotype rs11466749 of TSLP gene is the most common genotype in both monoorganic and polyorganic lesions in children with AtD. Its highest incidence was recorded in the phenotype of complete polyorganic lesion — AD+AR/ARC+BA. Variant A/G SNV rs11466749 of TSLP gene significantly increases the risk of developing the monoorganic phenotype of BA by 4.93 times and polyorganic BA+AR/ARC by 3.89 fold related to the complete polyorganic phenotype AD+AR/ARC+BA. Variant A/G SNV rs11466749 of TSLP gene significantly decreases the risk of developing the complete poliorgan phenotype AD+AR/ARC+BA by 3.23 and 4.17 fold related to the monоorganic phenotype of AD and polyorganic AD+AR/ARC respectively. Variant A/G SNV rs11466749 of TSLP gene with a tendency to statistical significance increases by 3.44 fold the risk of developing the monoorganic phenotype of AR/ARC related to the complete polyorganic phenotype AD+AR/ARC+BA. Variant A/A SNV rs11466749 of TSLP gene with a tendency to significance increases the risk of developing the complete polyorganic phenotype AD+AR/ARC+BA by 2.71 and 2.64 fold related to the monоorganic phenotype of AD and polyorganic AD+AR/ARC respectively. Variant A/A SNV rs11466749 of TSLP gene with a tendency to significance decreases by 3.03 fold the risk of developing the monoorganic phenotype of AD related to the complete polyorganic phenotype AD+AR/ARC+BA. Conclusions. Genotypic variants of the rs11466749 of TSLP gene play antagonistic roles in children: A/A significantly increases and A/G significantly decreases the risk of developing a common AtD phenotype. Determination of genotype variants A/A, A/G and G/G SNV rs11466749 of TSLP gene in children allows to personalize and increase the efficiency of predictive AtD diagnostics in children with mono- and polyorganic lesion phenotypes. 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 all participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interest was declared by the authors. Key words: atopic diseases, children, single nucleotide variants, thymic stromal lymphopoetin, monoorganic lesions, polyorganic lesions.