Role of Xenobiotic Detoxification System Gene Polymorphism in the Pathogenesis of Cutaneous Leishmaniasis
AbstractTreatment of patients with cutaneous leishmaniasis presents certain difficulties and, despite the standard therapy, rehabilitation from leishmanial and epithelization of the ulcers formed is significantly lengthened. This situation is largely due to the genetically determined polymorphism of certain genes, in particular, xenobiotic detoxification genes, which are able to accelerate or slow the removal of xenobiotics from the body of patients, which naturally affects the therapeutic effectiveness of the agents used. For the first time, studies were carried out on the detoxification genes of xenobiotics belonging to the cytochrome P-450, which are responsible for the functioning of this liver system. It should be noted that cytochrome P-450 (CYP2D6) metabolizes about 20 all known drugs.Taking into account that most Asians belong to slow metabolizers on this enzyme, there is an obvious need for genetic testing of CYP2D6 in Uzbekistan in order to correct doses of drugs. Variant CYP2D6 100C>T is a defining mutation for the haplotype CYP2D6*10, and is also common in the haplotype CYP2D6*4.Studies were carried out in 266 patients with cutaneous leishmaniasis when primers NCB1 design tools were used, which made it possible to study the C>T polymorphism of the CYP2D6 gene. DNA isolation was carried out by the Ribo-Prep application method (AmpliSens, Russia). Further, the isolated DNA was undergone to the examination of qualitative and quantitative characteristics on 1% agar gel by spectrophotometry. The distribution of genotypes according to polymorphism CYP2D6 100C>T showed a wild-type allele © frequency of 74% and a minor allele (T) frequency of 26%. Among 266 patients with cutaneous leishmaniasis, the CYP2D6*10 C>T gene was distributed as follows: the SS genotype was registered in 175 of 266 (65.7%) patients, the CT genotype in 84 (31.5%) and the TT genotype in 7 (2.6%) patients. It should be pointed out that C-alleles were observed in 259 (74%) and T-alleles in 91 (26%), i.e., there is a predominance of C-alleles over T-alleles by about 2.8 times.Genetic studies on cytochrome P-450 have shown that 34.1% of patients with cutaneous leishmaniasis show a decrease in the activity of the enzyme system of the CYP2D6 gene, which leads to a slowdown in the excretion of xenobiotics and, therefore, increases the risk of endogenous intoxication and torpidity with respect to the treatment. To eliminate these special inducers of cytochrome P-450, which are most hepatic drugs and systemic enzymothrepy.