Polymorphism of genes related to antioxidant defense systems, xenobiotic biotransformation, and immune regulation in allergic diseases: An observational case-control study

Background. Numerous studies indicate the multifactorial genesis of allergic diseases, which development and manifestation are underpinned by both endogenous and exogenous factors. Genetic predisposition is considered significant among the endogenous factors. The existing genetic research often presents contradictory findings and population-specific characteristics, thereby prompting further investigation into the role of polymorphism in the genes of body defense and adaptation systems in the pathogenesis of allergic diseases with pollinosis among them. Objective . To study the distribution characteristics of certain polymorphic loci of genes involved in the antioxidant defense system and biotransformation of xenobiotics (superoxide dismutase, glutathione transferase), pro-/anti-inflammatory cytokines as genetic risk factors influencing the onset and characteristics of pollinosis. Methods . An observational prospective case-control study involved patients from regional allergy centers (Ochapovsky Regional Clinical Hospital No. 1 and the Outpatient Department of the Regional Clinical Hospital No. 2, Krasnodar Krai, Russia). Additionally, the study enrolled 1st to 6th-year students of the Kuban State Medical University, who suffer from seasonal allergies. The study was carried out during the acute period of the disease, from February 20, 2023 to May 31, 2024. Based on clinical and anamnestic data, laboratory analysis results, and questionnaires considering the aforementioned compliance criteria, two study groups were formed depending on the disease course and its severity. Group 1 comprised patients diagnosed with allergic rhinitis ( n = 55), group 2 included patients with a diagnosis of allergic rhinitis in combination with bronchial asthma ( n = 35). In addition, a control group ( n = 61) was formed from individuals undergoing preventive medical check-ups in specified organizations, as well as from allergy-free 1st to 6th-year students of the Kuban State Medical University. The distribution of genotypes of polymorphic variants of the following genes: -58 T>C SOD2, - 313 A>G GSTP1, -308 G> А TNF-α, -592 C>A IL-10 among the study groups was considered a primary outcome measure of the study. Additional study parameters included indicators of the antioxidant system and lipid peroxidation, which were determined in order to evaluate the pathogenetic role of polymorphic variants of the studied genes in the patients (activity of the enzymes superoxide dismutase, glutathione transferase, and the level of malondialdehyde). Statistical analysis was performed using the Jamovi 2.3 (2022) software (Jamovi Project, Australia). Differences were considered statistically significant at p < 0.05. Results. The study established the metabolic shifts in the pro-/antioxidant system, leading to a condition characterized as oxidative stress in the study group of patients. An analysis of the distribution of genotypes for the -58 T>C SOD2 polymorphism gene revealed that the heterozygous TC genotype was more frequently observed in the allergic rhinitis group ( p < 0.001, odds ratio = 8.636; 95% confidence interval: 2.99–24.91) and in the group of patients with allergic rhinitis combined with bronchial asthma ( p < 0.05, odds ratio = 3.75; 95% confidence interval: 1.30–10.86). The mutant genotype polymorphism - 313A>G GSTP1 gene was characteristic of patients in the allergic rhinitis group ( p < 0.05, odds ratio = 5.25; 95% confidence interval: 1.26–21.86). The predominance of the GA genotype of the - 308 G> А TNF-α gene polymorphism was characteristic of patients in all study groups ( p < 0.001, odds ratio = 22.53; 95% confidence interval: 8.34–60.83 for allergic rhinitis; odds ratio = 15.88; 95% confidence interval: 5.48–45.99 for allergic rhinitis combined with bronchial asthma). Conclusion. The identification of gene polymorphisms related to body defense and adaptation systems, namely, -58 T>C SOD2, -313A>G GSTP1, -308 G> А TNF-α in individuals suffering from pollinosis obtains high predictive potential for disease development, its course, and guiding treatment strategies.