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UDK: 616.2 DOI:10.33920/MED-12-2312-02

Features of the frequency distribution of alleles and genotypes of the IL5 gene polymorphism rs2069812 in various phenotypes of bronchial asthma of professional genesis

Sergey Anatolievich Babanov PhD in Medicine, professor, head 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 Russia, 89, Chapaevskaya str., Samara, 443099, Russia, https://orcid.org/0000‑0002‑1667‑737X, e-mail: s.a.babanov@mail.ru
Antonina Gennadievna Baykova assistant professor 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 Russia, 89, Chapaevskaya str., Samara, 443099, Russia, https://orcid.org/0000‑0003‑3438‑6602, e-mail: a.s.bajkova@samsmu.ru
Leonid Aleksandrovich Strizhakov PhD in Medicine, professor of the Department of Internal and Occupational Diseases and Rheumatology, FSAEI HE I. M. Sechenov First Moscow State Medical University (Sechenov University) of the Ministry of Health of Russia, 8, Trubetskaya str., bld. 2, Moscow, 119991, Russia, https://orcid.org/0000‑0002‑2291‑6453
Andrey Vladimirovich Melentiev PhD Candidate in Medicine, leading researcher, head of the Scientific Advisory Department with a day hospital, Institute of General and Occupational Pathology named after member of the Russian Academy of Medical Sciences A. I. Potapov, FBSI F. F. Erisman Federal Scientific Centre of Hygiene of Rospotrebnadzor, 2, Semashko str., Mytishchi, 141014, Moscow Region, Russia, e-mail: amedik@yandex.ru
Anna Sergeevna Agarkova laboratory assistant 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 Russia, 89, Chapaevskaya str., Samara, 443099, Russia
Irina Nikolaevna Vasina assistant professor 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 Russia, 89, Chapaevskaya str., Samara, 443099, Russia, e-mail: shchepotevai@mail.ru

Despite the fact that occupational bronchial asthma has long been considered as a separate, independent disease, in recent years, more and more attention has been paid to its heterogeneity. Phenotyping of occupational asthma was initially based on identifying combinations of clinical characteristics of the disease, but now an increasing amount of data is emerging making it possible to understand the cause of clinical differences at the molecular genetic level. Thus, molecular genotyping opens up new opportunities in the search for a more targeted and personalized approach to the treatment of occupational bronchial asthma, as well as in the development of an individual strategy for its prevention. The purpose of the study is to determine genetic markers of the risk of developing occupational asthma under conditions of exposure to sensitizing substances by assessing the IL5 rs2069812 polymorphism. 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 Russia, and the Department of Occupational Pathology, Regional Center of Occupational Pathology, SBHI SR Samara Medical and Sanitary Unit No. 5 of the Kirov District. The study was carried out on 170 patients with various phenotypes of occupational bronchial asthma and 50 participants in the control group: group 1 (42 patients) — phenotype «occupational asthma, allergic form», group 2 (36 patients) — phenotype «occupational asthma, non-allergic form», group 3 (58 patients) — phenotype «occupational asthma — occupational chronic obstructive pulmonary disease», group 4 (34 patients) — phenotype «occupational asthma — metabolic syndrome», group 5 — control group (healthy), 50 participants. As part of the study of genetic predisposition to occupational bronchial asthma, IL5 rs2069812 polymorphism was determined. DNA samples were isolated from peripheral venous blood lymphocytes using phenol-chloroform extraction. Genotyping was performed by real-time polymerase chain reaction using primers and probes designed using PrimerQuest (Integrated DNA Technologies, Inc.). Results. Thus, for the first time, the genetic markers of the risk of occupational asthma under exposure to sensitizing substances, i.e. IL5 rs2069812 polymorphism, have been identified, which makes it possible to recommend the determination of this genetic marker during indepth periodic medical examinations of individuals working under conditions of exposure to sensitizing and irritating substances in the presence of clinical, functional, and immunological changes. Conclusion. The identified marker profiles of genotypes of occupational bronchial asthma can optimize the approach to diagnosis, treatment, and prevention of this pathology, as well as expand the range of criteria for predicting the course of the disease. When IL-5 polymorphism is detected during molecular genetic studies, patients need to be linked to care and undergo repeated pulmonary function tests once every 6 months and in-depth periodic medical examinations in a specialized occupational pathology center with the mandatory participation of a pulmonologist, allergist/immunologist, and occupational pathologist, as well as with conducting extended functional and immunological studies once every 2 years.

В настоящее время под диагнозом «профессиональная бронхиальная астма» (ПБА) понимается заболевание дыхательных путей хронического характера, которое характеризуется обратимой обструкцией и/или гиперреактивностью бронхов, проявляется эпизодами (приступами) удушья, свистящими хрипами в груди, кашлем, обусловленными развитием воспалительного ответа на экспозицию специфического профессионального агента (промышленной пыли, газов, аэрозолей или веществ токсико-аллергенного действия) [1, 2]. При этом, несмотря на то что профессиональная бронхиальная астма в длительное время рассматривалась как отдельное, самостоятельное заболевание, в последнее время все больше внимания уделяется его неоднородности и гетерогенности [3–5]. В настоящее время установлено, что активность воспалительного процесса, тяжесть течения и прогноз заболевания при профессиональной бронхиальной астме не всегда представляется возможным оценить только на основании стандартных клинических и лабораторных методов исследования. В патогенезе профессиональной бронхиальной астмы, как в мультифакториальном заболевании, участвует несколько сложных взаимосвязанных полиморфных генетико-биохимических систем, а также учитываются индивидуальные особенности организма, что делает актуальным изучение и поиск информативных маркеров различных форм профессиональной бронхиальной астмы, при этом актуальным является не только изучение количественного уровня воспалительных маркеров, но и соотношение аллельных вариантов их генов, характеризующих генетически запрограммированную продукцию того или иного элемента воспаления, определяющих направленность воспалительных и аллергических реакций [6–8]. Таким образом, молекулярное генотипирование открывает новые возможности в поиске более целенаправленного и персонализированного подхода к терапии профессиональной бронхиальной астмы, а также в разработке индивидуальной стратегии ее профилактики [9–12].

Цель исследования — определение генетических маркеров риска развития профессиональной бронхиальной астмы в условиях воздействия сенсибилизирующих веществ при помощи оценки полиморфных вариантов rs2069812 гена IL-5.

For citation:
Sergey Anatolievich Babanov, Antonina Gennadievna Baykova, Leonid Aleksandrovich Strizhakov, Andrey Vladimirovich Melentiev, Anna Sergeevna Agarkova, Irina Nikolaevna Vasina, Features of the frequency distribution of alleles and genotypes of the IL5 gene polymorphism rs2069812 in various phenotypes of bronchial asthma of professional genesis. Therapist. 2023;12.
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