Lebid L. V., Kireev I. V., Ljashenko A. A.

FEATURES OF THE GENETIC POLYMORPHISM OF ARYLAMINE N-ACETYLTRANSFERASE 2 IN PATIENTS WITH PULMONARY TUBERCULOSIS IN KHARKIV REGION

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About the author:	Lebid L. V., Kireev I. V., Ljashenko A. A.
Heading	CLINICAL MEDICINE
Type of article	Scentific article
Annotation	Tuberculosis is still one of the main public health problem worldwide. Various studies of single nucleotide polymorphism (SNP) of arylamine N-acetyltransferase 2 (NAT2) in tuberculosis patients in different populations are carried out to determine the probability of developing the disease and metabolic features of anti-TB drugs. It is relevant to using the SNP to predict not only the possibility of developing the disease beforehand, but also to predict the severity and characteristics of its course, than is necessary for effective treatment. Objective. To study the genetic polymorphism of NAT2 in patients with pulmonary tuberculosis in the Kharkov region, Ukraine 5 SNPs of NAT2 were determined including C282T, C481T, G590A, A803G and G857A. Materials and methods. The research group consisted of 27 Caucasians with different types and prevalence of tuberculosis process, with different sensitivity of Mycobacterium tuberculosis to anti-TB drugs and different treatment efficacy. The molecular genetic study was carried out using a set of reagents for DNA extraction Diatom ™ DNA Prep 200 according to the manufacturer's instructions. Statistical analysis of the results of research carried out using SPSS 22. Results and discussion. The group surveyed included 27 patients, unrelated individuals, Caucasians: 22 men and 5 women. In 19 patients was installed newly diagnosed pulmonary tuberculosis. One patient had recurrent pulmonary tuberculosis. In 7 patients - chemoresistant pulmonary tuberculosis: from 5 - multidrug-resistant tuberculosis (MDR-TB) and 2 - with enhanced resistance tuberculosis (XDR-TB). All 27 patients were found the same combination of mutations 282C / T, 481C / T, 590G / A, in which were found only heterozygotes, whereas among genotypes A803G, G857A were met both heterozygotes and homozygotes. Significant differences were obtained only for genotype A803G. Revealed that all patients with "wild" type 803A (100%) had extensive tuberculosis with the defeat of both lungs, whereas heterozygotes A803G in 54.5% of cases had the process limited in one lung, the mutant homozygotes 803GG - 50% of cases (p <0, 05). All patients homozygotes as a "wild" type 803A, and the mutated 803 GG were smear positive. Heterozygotes A803G were smear positive in 36.4% (p <0,05). Comparative analysis of the effectiveness of treatment in patients with sensitive Mycobacterium tuberculosis, MDR-TB and XDR-TB with different genetic polymorphism NAT2 has not set significant differences. Conclusions:1. In the Caucasian population of Kharkiv region, Ukraine there is no association of polymorphic variants C282T, S481T, G590A and G857A gene NAT2 with clinical manifestations of pulmonary tuberculosis. 2. "Wild" type 803A is associated with a predisposition to severe extensive forms of the smear positive tuberculosis.
Tags	pulmonary tuberculosis, NAT2, gene polymorphism
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Publication of the article	«World of Medicine and Biology» №1(48), 2015 year, 043-046 pages, index UDK 616.24-002.5:615.28