Prevention of adverse reactions due to pharmacotherapy in MRTB considering polymorphism of glutathione-S-transferase M1 and T1genes

2019 
Relevance: Genetics of widespread human diseases is a branch of research which is actively developing. The study of polymorphisms of known candidate genes and their prognostic impact on the disease, is one of the important tasks in the study of tuberculosis. Objective: To prevent the development of adverse reactions due to pharmacotherapy in multi-drug resistant tuberculosis considering deletion polymorphism of the genes in the detoxification system of glutathione-S-transferase xenobiotics. Subject: We have examined 100 patients with newly diagnosed multidrug-resistant uberculosis (MDR-TB). Methods: Polymorphism GSTM1 and GSTM1 areas were isolated using complex multi PCR for M. Arana et all (1996). Results: With null genotype (especially for gene GSTM1) in the haplotype (GSTM1 + / GSTT1 0/0, GSTT1 + / GSTM1 0/0, GSTT1 0/0 / GSTM1 0/0) the development of adverse reactions to the second-line antimycobacterial drugs occurred reliably more frequently by 26,8% (χ2 = 3,41, p = 0.049) and to the absence of bacterial suspension in the 240th dose by 35.2% (p = 0.006), respectively. In a favorable combination of functional alleles of analyzed genes (GSTM1 + / GSTT1 +) reliably less frequent were nausea and vomiting after taking AMBD, insomnia, dizziness, pain in joints and muscles, itching, rash, headache, edema, fever (p Conclusions: Deletion in the promoter area of the analyzed genes increases the risk of adverse reactions to antimycobacterial drugs and reduces the effectiveness of treatment in patients with MDR TB by 16.6 times [OR = 24,50, 95% CI OR: 2,18-142 64, p = 0.009].
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