TY - JOUR

T1 - Роль полиморфных вариантов генов аргиназ (ARG1, ARG2), участвующих в метаболизме бета-2-агонистов, в развитии и течении бронхиальной астмы

AU - Савельева, Ольга Николаевна

AU - Карунас, Александра Станиславовна

AU - Федорова, Юлия Юрьевна

AU - Хуснутдинова, Эльза Камилевна

N1 - Funding Information: The study was carried out with the financial support of the Russian Foundation for Basic Research (grant No. 17-04-02195 and No. 19-315-90055), state assignment of the Ministry of Education and Science of the Russian Federation (No. AAA-A16-116020350032-1). DNA samples were used from the?Collection of human biomaterials IBG UFRC RAS?, supported by the Program of bioresource collections of the FASO of Russia (agreement No. 007-030164/2). Publisher Copyright: © 2020 Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of Sciences. All rights reserved.

PY - 2020

Y1 - 2020

N2 - 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 ARG1and ARG2genes 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.

AB - 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 ARG1and ARG2genes 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.

KW - Arginase 1 (ARG1)

KW - Arginase 2 (ARG2)

KW - Association

KW - Asthma

KW - Beta-2-agonists

KW - Predisposition genes

KW - ASSOCIATION

KW - BRONCHODILATOR RESPONSE

KW - arginase 1 (ARG1)

KW - arginase 2 (ARG2)

KW - association

KW - asthma

KW - beta-2-agonists

KW - predisposition genes

KW - Predisposition genes

KW - Arginase 1 (ARG1)

KW - Arginase 2 (ARG2)

KW - Asthma

KW - Association

KW - Beta-2-agonists

UR - http://www.scopus.com/inward/record.url?scp=85087826286&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/7a385a5a-a1c4-3c82-91af-2716c15fd38d/

U2 - 10.18699/VJ20.631

DO - 10.18699/VJ20.631

M3 - статья

VL - 24

SP - 391

EP - 398

JO - Вавиловский журнал генетики и селекции

JF - Вавиловский журнал генетики и селекции

SN - 2500-0462

IS - 4

ER -