Genotype-associated clinical markers of atopic phenotype development in children

Abstract

Atopic march (AM) occurs as the linear progression of atopic disorders (AtD) from atopic dermatitis (AD) phenotype to its combinations with other AtD: allergic rhinitis/rhinoconjunctivitis (AR/ARC) and bronchial asthma (BA). Thymic stromal lymphopoietin (TSLP) plays an important role in AtD pathogenesis. Single nucleotide variant (SNV) rs11466749 of the TSLP gene during the last decades showed the controversial roles of A/A, A/G and G/G genotypes in occurrence of the mono- and polyorgan AM phenotypes in children. Purpose - to determine the associations and risks of AM phenotypes with homozygous or heterozygous SNV rs11466749 genotypes of the TSLP gene in children. Materials and methods. The study involved 398 children aged 3 to 18 years old: 293 children in the main group and 105 - in the control group. Patients of the main group suffered from AtD in 6 different AM phenotypes: «AD», «AR\ARC», «BA», «AD+AR/ARC», «BA+AR/ARC», «AD+AR/ARC+BA»; patients of the control group suffered from gastrointestinal pathology. Patients of all cohorts were genotyped for genotype variants A/A, A/G and G/G rs11466749 TSLP by the polymerase chain reaction in real time. Pearson’ contingency coefficient (rb), Pearson test (ꭕ2), Fisher’s exact test, odds ratio (OR) with a 95% confidence interval (95% CI) were used for statistical processing of the obtained results. Results at p≤0.05 were considered statistically significant. Results. The homozygous A/A rs11466749 TSLP genotype was significantly most frequent in phenotypes with mono- or oligoorgan affection «AR/ARC» and polyorgan affection «BA+AR/ARC» and «AD+AR/ARC+BA»: 66,2%, 65.3% and 76.9% respectively (p<0.05). Heterozygous genotype A/G rs11466749 TSLP was the second most significant and frequent: «AR/ARC» - 31.0% (p<0.05), «BA+AR/ARC» - 31.9% (p=0.05-0.1) and «AD+AR/ARC+BA» - 11.5% (p<0.05). Genotype A/A rs11466749 TSLP was significantly associated and increased the development risks of the 3 specified AM phenotypes: «AR/ARC» - rb=0.156, OR=1.92 (95% CI: 1.03-3.58, p<0.05); «BA+AR/ARC» - rb=0.147, OR=1.84 (95% CI: 1.0-3.42, p<0.05); «AD+AR/ARC+BA» - rb=0.212, OR=3.27 (95% CI: 1.22-8.80, p<0.05). Genotype A/G rs11466749 TSLP was reliably associated and had a protective effect on the development of bespoke AM phenotypes: «AR/ARC» - rb=0.148, OR=0.53 (95% CI: 0.28-1.0, p<0.05); «BA+AR/ARC2 - rb=0.138, OR=0.55 (95% CI: 0.30-1.04, p=0.05-0.1); «AD+AR/ARC+BA» - rb=0.280, OR=0.15 (95% CI: 0.04-0.55, p<0.05). Conclusions. The homozygous genotype A/A SNV rs11466749 of TSLP gene significantly increases the risk of developing AM phenotypes «AR/ARC», «BA+AR/ARC» and «AD+AR/ARC+BA», and the heterozygous genotype A/G SNV rs11466749 of TSLP gene possesses a significantly protective effect on their development in children. 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 patient was obtained for conducting the studies. No conflict of interests was declared by the author.