Association of T102C (rs6313) serotonin receptor gene HTR2A polymorphism with the development of anxiety, depressive disorders in children with organic and functional respiratory pathologies

Abstract

Purpose - to establish the relationship between the polymorphism T102C (rs6313) of the HTR2A serotonin receptor gene and the risk of developing somatoform and comorbid anxiety and depressive disorders in children with respiratory pathologies.

Materials and methods. The study involved 90 patients, whose average age was 11.6±3.3 years (M±σ), of whom 63.3% were boys (n=57) and 36.7% were girls (n=33). The patients were divided into three groups of 30 (33.3%) people in each: with bronchial asthma (BA), with pneumonia, and with somatoform autonomic dysfunction of the respiratory system (SАDRS). Also, 30 healthy children of the control group were examined. The Children’s depression inventory M. Kovacs (1992), questionnaire was used to detect depression, and the Spielberger-Hanin test-questionnaire was used to study anxiety. In all children, serotonin and gamma aminobutyric acid concentrations in blood serum were determined by the ELISA method. Genetic studies were carried out with the determination of the T102C (rs6313) serotonin receptor 5-HTR2A genetic polymorphism by polymerase chain reaction. Statistical analyses were performed to determine the absolute and attributable risk, odds ratio (OR) and relative risk, and the potential harm index. The significance of differences was assessed using the two-sample Student’s t-test and the construction of a 95% confidence interval (CI) for the difference in means, as well as Fisher’s exact test, χ² with Yates’ correction, and Pearson's coefficient. Values with p<0.05 were considered significant.

Results. In general, sick carriers of the T/T allele have the highest level of personal anxiety of 46.9±8.9 points, reaching the lowest level in sick carriers of the C/C allele of 41.6±8.5 points (95% CI: 0.13-10.47; p˂0.045). The highest level of personal anxiety was also observed in patients carrying the T/T allele with SАDRS (52.3±6.3 points), reaching the lowest level in patients carrying the C/C allele - 44.8±7.7 points (95% CI: 0.26-14.7; p˂0.05). The presence of the T/T allele increases, on average, the incidence of anxiety disorders in patients with SАDRS by 41.7±16.0%, while the OR is 7.00 (95% CI: 1.38-35.47) and anxiety disorders and SАDRS in patients with BA by 44.2±16.0%, while the OR is 8.10 (95% CI: 1.61-40.76). In general, the level of serotonin in patients with respiratory pathologies with the presence of the T/T allele was lower compared to the presence of the C/C allele (95% CI: 0.084-0.656 μmol; p˂0.012).

Conclusions. The presence of the T/T polymorphism is a predictor of the development of SАDRS and anxiety disorders in children (p=0.021) and increases the incidence of SАDRS and anxiety disorders in patients with BA (p=0.010), probably due to disruption of serotonin metabolism.

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 authors.