Analysis of the association of bronchial asthma clinical course with ER22/23EK and TTH111I polymorphic variants in the glucocorticoid receptor gene
Authors: Kachkovska Vladyslava 
Published: December 2023

bronchial asthma (BA) is one of the important and urgent medical and social problems ofour time due to the high incidence and prevalence, which keep increasing. This is a typical multifactorialdisease determined by the influence of external factors and genetic predisposition. The combination ofthese numerous factors determines the phenotypic heterogeneity of bronchial asthma. Identification ofasthma phenotypes was based mainly on clinical variables; however, further identification of clinicalphenotypes revealed their genetic heterogeneity. Accordingly, the determination of genetic marker datafor clinical phenotypes of bronchial asthma will improve the diagnostic capabilities of preventive andevidence-based medicine in the future. The objective of the study was to determine the features of thecourse of early-onset and late-onset BA depending on the ER22/23EK and Tth111I polymorphisms inthe glucocorticoid receptor gene and to supplement modern data on the role of genetic factors in BAonset and the severity for various phenotypes. We examined 553 BA patients and 95 apparently healthyindividuals. All of them had previously signed an informed consent form. BA diagnosis, severity, andcontrol level were determined according to the GINA recommendations-2016 and its later versions andthe Decree of the Ministry of Health of Ukraine No. 868 issued on 08 October 2013. Respiratory functionwas studied using Kardioplius diagnostic suite (Ukraine). The patients were divided into two clinicalgroups according to the BA onset: Group I included 282 patients with late-onset asthma, and GroupII included 271 patients with early-onset asthma. The Bioethics Committee of the Medical Institute ofSumy State University approved the study. The ER22/23EK (rs 6189/6190) and Tth111I (rs10052957)polymorphic variants in the glucocorticoid receptor (GR) gene were determined using polymerase chainreaction-restriction fragment length polymorphism analysis. Statistical analysis of obtained results wasperformed using SPSS–17 program. A statistically significant difference was observed in the distributionof genotypes for the ER22/23EK and TthIIII polymorphisms in the GR gene depending on BA severity,with a higher frequency of minor alleles in both cases in patients with severe BA (χ2 = 6.09; р = 0.048and χ2 = 15.8; р = 0.001, respectively). The relative risk of severe BA did not depend on the ER22/23EKpolymorphism in the GR gene; however, it was 3.63 times higher in the carriers of the TT genotype forthe Tth111I polymorphism vs. carriers of the major allele homozygotes. The risk of severe disease inearly-onset and late-onset BA depended on the Tth111I polymorphism in the GR gene; in the recessivemodel, it increased by 3.7 times for early-onset asthma and by 3.5 times – for late-onset asthma. Analysis
of ER22/23EK (rs 6189/6190) and Tth111I (rs10052957) polymorphic variants in the GR gene demon-strated their possible correlation not only with the increased risk of BA, but also with certain phenotypes
and severity of the disease.