vavilovВавиловский журнал генетики и селекцииVavilov Journal of Genetics and Breeding2500-3259Institute of Cytology and Genetics of Siberian Branch of the RAS10.18699/VJ20.631vavilov-2648Research ArticleБИОТЕХНОЛОГИЯ В ПОСТГЕНОМНУЮ ЭРУMEDICAL GENETICSРоль полиморфных вариантов генов аргиназ (ARG1, ARG2), участвующих в метаболизме бета-2-агонистов, в развитии и течении бронхиальной астмыThe role of polymorphic variants of arginase genes (ARG1, ARG2) involved in beta-2-agonist metabolism in the development and course of asthmahttps://orcid.org/0000-0002-9690-1481СавельеваО. Н.SavelievaO. N.

Уфа

Ufa

olyasavelie@yandex.ruhttps://orcid.org/0000-0002-2570-0789КарунасА. С.KarunasA. S.

Уфа

Ufa

carunas@list.ruhttps://orcid.org/0000-0002-9344-828XФедороваЮ. Ю.FedorovaYu. Yu.

Уфа

Ufa

МурзинаР. Р.MurzinaR. R.

Уфа

Ufa

СавельеваА. Н.SavelievaA. N.

Уфа

Ufa

ГатиятуллинР. Ф.GatiyatullinR. F.

Уфа

Ufa

https://orcid.org/0000-0003-1371-7927ЭткинаЭ. И.EtkinaE. I.

Уфа

Ufa

https://orcid.org/0000-0003-2987-3334ХуснутдиноваЭ. К.KhusnutdinovaE. K.

УфаСанкт-Петербург

UfaSt. Petersburg

Башкирский государственный университетРоссияBashkir State UniversityRussian FederationБашкирский государственный университет; Институт биохимии и генетики – обособленное структурное подразделение Уфимского федерального исследовательского центра Российской академии наукРоссияBashkir State University; Institute of Biochemistry and Genetics – Subdivision of the Ufa Federal Research Centre of the Russian Academy of SciencesRussian FederationИнститут биохимии и генетики – обособленное структурное подразделение Уфимского федерального исследовательского центра Российской академии наукРоссияInstitute of Biochemistry and Genetics – Subdivision of the Ufa Federal Research Centre of the Russian Academy of SciencesRussian FederationБашкирский государственный медицинский университет Министерства здравоохранения Российской ФедерацииРоссияBashkir State Medical University of the Ministry of Healthcare of the Russian FederationRussian FederationИнститут биохимии и генетики – обособленное структурное подразделение Уфимского федерального исследовательского центра Российской академии наук; Санкт-Петербургский государственный университетРоссияInstitute of Biochemistry and Genetics – Subdivision of the Ufa Federal Research Centre of the Russian Academy of Sciences; St. Petersburg State UniversityRussian Federation202002072020244391398Copyright © Савельева О.Н., Карунас А.С., Федорова Ю.Ю., Мурзина Р.Р., Савельева А.Н., Гатиятуллин Р.Ф., Эткина Э.И., Хуснутдинова Э.К., 20202020Савельева О.Н., Карунас А.С., Федорова Ю.Ю., Мурзина Р.Р., Савельева А.Н., Гатиятуллин Р.Ф., Эткина Э.И., Хуснутдинова Э.К.Savelieva O.N., Karunas A.S., Fedorova Y.Y., Murzina R.R., Savelieva A.N., Gatiyatullin R.F., Etkina E.I., Khusnutdinova E.K.This work is licensed under a Creative Commons Attribution 4.0 License.https://vavilov.elpub.ru/jour/article/view/2648

Бронхиальная астма (БА) – широко распространенное тяжелое заболевание дыхательных путей, которое при недостаточно эффективном лечении приводит к значительному ухудшению качества жизни пациентов. Отсутствие контроля над симптомами БА ведет к быстрому прогрессированию, утяжелению заболевания и инвалидизации пациентов. Чувствительность к лекарственной терапии БА во многом зависит от взаимодействия генетических и эпигенетических факторов, которые на 50–60 % определяют вариабельность терапевтического ответа пациентов. Одной из основных групп препаратов, используемых для лечения БА, являются бета-2-агонисты, оказывающие значительное бронходилатирующее действие. По литературным данным, аллельные варианты генов аргиназ ARG1 и ARG2 ассоциированы с риском развития БА, показателями спирографии и эффективностью терапии бронходилататорами. Повышенная экспрессия генов аргиназ ведет к снижению биодоступности L-аргинина и уровня оксида азота в организме и, как следствие, к увеличению степени воспаления и ремоделирования дыхательных путей. Выполнено исследование полиморфных вариантов генов аргиназ (rs2781667 гена ARG1 и rs17249437, rs3742879, rs7140310 гена ARG2) у 236 детей, больных БА, а также у 194 неродственных здоровых индивидов русской, татарской и башкирской этнической принадлежности, проживающих на территории Республики Башкортостан. Проведен поиск ассоциаций изученных полиморфных вариантов с развитием, течением БА и чувствительностью к терапии у пациентов с БА. Установлено, что аллель rs2781667*С гена ARG1 является маркером повышенного риска развития БА у татар. В группе русских пациентов с БА генотипы rs17249437*TT и rs3742879*GG гена ARG2 ассоциированы со снижением показателей спирографии (ОФВ1, МОС25). У русских и татар, находящихся на монотерапии ингаляционными глюкокортикостероидами или на комбинированной терапии, показана ассоциация аллеля rs17249437*Т и генотипа rs17249437*TT гена ARG2 с частично контролируемым и неконтролируемым течением астмы.

Asthma is a common severe disease of the respiratory tract, it leads to a significant impairment in the quality of a patient’s life unless effectively treated. Uncontrolled asthma symptoms are a cause of disease progression and development, they lead to an increase in the patient’s disability. The sensitivity to asthma therapy largely depends on the interaction of genetic and epigenetic factors, which account for about 50–60 % of variability of therapeutic response. Beta-2-agonists are some of the major class of bronchodilators used for asthma management. According to published data, allelic variants of the arginase ARG1 and ARG2 genes are associated with a risk of asthma development, spirometry measures and efficacy of bronchodilator therapy. High arginase activity results in a low level of plasma L-arginine and in a decrease in nitric oxide, and, as a result, in an increase in airway inflammation and remodeling. Arginase genetic polymorphisms (rs2781667 of the ARG1 gene, rs17249437, rs3742879, rs7140310 of the ARG2 gene) were studied in 236 children with asthma and 194 unrelated healthy individuals of Russian, Tatar and Bashkir ethnicity from the Republic of Bashkortostan. Association analysis of the studied polymorphisms with asthma development and course, the sensitivity to therapy in patients was carried out. It was found that the rs2781667*C allele of the ARG1 gene is a marker of an increased risk of asthma in Tatars. In Russians, the association of rs17249437*TT and rs3742879*GG genotypes of the ARG2 gene with a decrease in spirometry measures (FEV1, MEF25) was established. In Russians and Tatars receiving glucocorticoid monotherapy or combination therapy, the association of the rs17249437*T allele and rs17249437*TT genotype of the ARG2 gene with a partially controlled and uncontrolled course of asthma was shown.

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The authors declare that there are no conflicts of interest present.