Savelieva O N, Karunas A S, Fedorova Yu Yu, Murzina R R, Savelieva A N, Gatiyatullin R F, Etkina E I, Khusnutdinova E K
Bashkir State University, Ufa, Russia.
Bashkir State University, Ufa, Russia Institute of Biochemistry and Genetics - Subdivision of the Ufa Federal Research Centre of the Russian Academy of Sciences, Ufa, Russia.
Vavilovskii Zhurnal Genet Selektsii. 2020 Jul;24(4):391-398. doi: 10.18699/VJ20.631.
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 rs2781667C allele of the ARG1 gene is a marker of an increased risk of asthma in Tatars. In Russians, the association of rs17249437TT and rs3742879GG 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 rs17249437T allele and rs17249437*TT genotype of the ARG2 gene with a partially controlled and uncontrolled course of asthma was shown.
哮喘是一种常见的严重呼吸道疾病，除非得到有效治疗，否则会严重损害患者的生活质量。未得到控制的哮喘症状是疾病进展和发展的原因，会导致患者残疾增加。哮喘治疗的敏感性很大程度上取决于遗传和表观遗传因素的相互作用，这约占治疗反应变异性的50-60%。β-2-激动剂是用于哮喘管理的一些主要支气管扩张剂类别。根据已发表的数据，精氨酸酶ARG1和ARG2基因的等位基因变体与哮喘发展风险、肺功能测定指标以及支气管扩张剂治疗的疗效相关。高精氨酸酶活性导致血浆L-精氨酸水平降低和一氧化氮减少，结果导致气道炎症和重塑增加。在来自巴什科尔托斯坦共和国的236名哮喘儿童和194名俄罗斯、鞑靼和巴什基尔族裔的无关健康个体中，研究了精氨酸酶基因多态性（ARG1基因的rs2781667、ARG2基因的rs17249437、rs3742879、rs7140310）。对所研究的多态性与哮喘发展和病程、患者对治疗的敏感性进行了关联分析。发现ARG1基因的rs2781667C等位基因是鞑靼人哮喘风险增加的标志物。在俄罗斯人中，确定了ARG2基因的rs17249437TT和rs3742879GG基因型与肺功能测定指标（第一秒用力呼气容积、25%最大呼气流量）降低相关。在接受糖皮质激素单一疗法或联合疗法的俄罗斯人和鞑靼人中，显示ARG2基因的rs17249437T等位基因和rs17249437*TT基因型与哮喘部分控制和未控制的病程相关。
