Genotypes and frequencies of the TSLP gene variant rs1837253 in different occupational asthma phenotypes

Abstract

Introduction. Currently, despite the fact that occupational asthma has long been considered as a separate, independent disease, recent studies pay more and more attention to its heterogeneity. Occupational asthma phenotyping was originally based on the identification of combinations of clinical characteristics of the disease, but now more and more data that allow understanding the cause of clinical differences at the molecular genetic level are emerging. Thus, molecular genotyping opens up new opportunities in the search for a more targeted and personalized approach to the treatment of occupational asthma, as well as in the development of an individual strategy for its prevention. The aim of the study was to determine the genetic risk markers for the development of oc cupational asthma under the influence of sensitizers by assessing the TSLP gene polymor phism rs1837253. Materials and methods. The study was conducted on the basis of the Department of Occupational Diseases and Clinical Pharmacology named after honored scientist of the Russian Federation professor V. V. Kosarev, FSBEI HE Samara State Medical University of the Ministry of Health of the Russian Federation, and the Department of Occupational Pathology, SBHI SR Samara Medical and Sanitary Unit No. 5 of the Kirovsky District. The study involved 170 patients with various phenotypes of occupational bronchial asthma (OBA) and 50 people in the control group: group 1 (42 people) — the phenotype «allergic occupational bronchial asthma», group 2 (36 people) — the phenotype «non-allergic occupational bronchial asthma», group 3 (58 people) — the phenotype «occupational bronchial asthma — occupational chronic obstructive pulmonary disease», group 4 (34 people) — the phenotype «occupational bronchial asthma — metabolic syndrome», group 5 (50 people) — the control group (healthy). As part of the study of genetic predisposition to occupational bronchial asthma,genetic polymorphisms of the rs1837253 TSLP gene were determined. DNA samples were isolated from peripheral venous blood lymphocytes by phenol-chloroform extraction. Genotyping was performed by real-time polymerase chain reaction using primers and probes developed with the PrimerQuest tool (Integrated DNA Technologies, Inc.). Results. Thus, for the first time, genetic risk markers for the development of occupational asthma under the influence of sensitizers have been identified: the TSLP gene polymorphisms rs1837253, which makes it possible to recommend determining these genetic markers during in-depth periodic medical examinations in persons working under exposure to sensitizing and irritating substances in the presence of clinical, functional, and immunological changes. Conclusion. The identified marker profiles of OBA genotypes can optimize the approach to the diagnosis, treatment and prevention of this pathology, as well as expand the range of criteria for predicting the course of the disease. If polymorphisms of the TSLP gene are detected during molecular genetic studies, patients need to be registered with a dispensary and require repeated examinations of the function of external respiration once every 6 months and in-depth periodic medical examinations in a specialized center of occupational pathology with the obligatory participation of a pulmonologist, an allergist-immunologist, an occupational pathologist, as well as conducting extended functional and immunological studies once every 2 years.