Анализ метилирования генов гистаминовых рецепторов HRH1 и HRH2 у больных бронхиальной астмой и здоровых индивидов

Abstract

Bronchial asthma is one of the most common chronic respiratory diseases. Histamine is a central mediator of inflammation which plays an important role in airway obstruction and bronchial secretion. Epigenetic studies of asthma patients confirm the association between the epigenetic regulation of gene expression and the pathogenesis of this disease. In recent years, an increasing number of differentially methylated CpG sites associated with the risk of asthma development and clinical course was identified. The aim of this work was to carry out a comparative analysis of the degree of methylation of the histamine receptor genes HRH1 and HRH2 promoter regions between with asthma patients and individuals of the control group from the Republic of Bashkortostan (RB). DNA samples isolated from the peripheral blood of 157 asthma patients and 155 controls under 18 years of age of Russian and Tatar ethnicity were used as the study material. MS-HRM analysis of the promoter region of the histamine receptor H1 gene HRH1 showed that the methylation level of this region varies from 90% to 100%. A significantly higher frequency of complete methylation (100%) of the promoter region of the HRH1 gene was found in patients with asthma compared to controls. MS-HRM analysis of the promoter region of the histamine receptor H2 gene HRH2 showed that the methylation level of this region was from 0% to 10%; no significant differences in the frequency of different methylation levels in asthma children and individuals from the control group were found. Thus, differential methylation of the promoter region of the HRH1 gene between asthma patients and controls was found confirming the involvement of the epigenetic mechanism of DNA methylation in the disease pathogenesis.