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Information × Registration Number 0219U000537, 0115U002944 , R & D reports Title Development of panel of pharmacogenetic markers for prognosis of the course and efficiency of treatment of social important human diseases at Ukrainian patients. popup.stage_title Head Livshits Ludmila Avramivna, Livshyts Liudmyla A., Registration Date 06-02-2019 Organization Institute of Molecular Biology and Genetics of NASU popup.description2 The aim of the study was: i) to investigate the influence of А46G (rs2400707) and C79G (rs1042713) ADRB2 gene polymorphisms on the severity of the disease progression determining by the treatment efficacy and its side effects, ii) to study the conformational and functional defects of the ?2-adrenergic receptor, caused by p.16Arg> Gly, p.27Gln> Glu and p.164Thr> Ile amino acid substitutions, and iii) to evaluate the effectiveness of salbutamol (a group of ?-agonists) in the treatment of children with bronchial asthma. The study group of patients (n=72) diagnosed with bronchial asthma and the database of patients' clinical data were created and characterized. Розроблено, оптимізовано та апробовано діагностичну методику аналізу поліморфізмі G46A (rs2400707) та С79G (rs1042713) гена ADRB2 з використанням алель-специфічної ПЛР з наступним аналізом поліморфізму довжини рестрикційних фрагментів (ПДРФ), яка дозволяє встановити не лише генотип індивіда за кожним з поліморфізмів, а й гаплотипи за ними. The diagnostic method based on allele-specific PCR with the following analysis of restriction fragment length polymorphism(RLFP) for the analysis of G46A (rs2400707) and C79G (rs1042713) ADRB2 gene polymorphisms was developed, optimized and tested, which allows to detect the patient's genotypes as well as haplotypes by the polymorphisms. The distribution of the genotypes alleles and haplotypes frequencies for the A46G (rs2400707) and C79G (rs1042713) polymorphisms of the of the ADRB2 gene in Ukrainian patients with different bronchial asthma types was obtained. It has been shown that the 46AA genotype, as well as the combined genotype 46AA + 79CC are predisposing factors for severe types of bronchial asthma (OR = 5.32; CI 95%: 1.04 - 27.25; p = 0.03). According to the in silico 3D modeling of mutant proteins encoded by ADRB2 gene with SNPs 46A> G, 79C> G and 491C> T and the molecular docking of the "wild type" protein and mutamt protein encoded by SNP 491C> T of the ADRB2 gene with salbutamol ligand it has been identified that substitutions 46A> G, 79C> G should be possible genetic markers of the bronchial asthma severity, and the substitution 491C> T should be possible pharmacogenetic marker of a poor patient response to salbutamole treatment. Thus, the bases of pharmacogenetic testing for the bronchial asthma treatment prognosis, which should implement an individual approach in the drugs and their dosage administration and predict disease pathogenesis and avoid mistakes in the treatment. Product Description popup.authors А.В. Маяковська В.М. Пампуха Л.А. Лівшиць М.В. Нечипоренко О.В. Городна Р.В.Гулковський С.А. Кравченко С.Ю.Чернушин popup.nrat_date 2020-04-02 Close