Assessment of Association Cytochrome Р450 Gene Polymorphism with Pathogenesis and Course of HСV in Uzbek Population

Aims: The assessment of polymorphisms CYP2C9*2 (430С>Т; rs1799853) and CYP2E1*1B (–C9896G, rs2070676) role of the genes of cytochrome Р450 in pathogenesis of the chronic viral hepatitis C (HCV) in Uzbek population became the main aim.

Place and Duration of Study: The molecular and genetic study of biomaterial was accomplished under Department of Molecular Medicine and Cellular Technologies of SRIH&BT (Scientific Research Institute of Hematology and Blood Transfusion), MoH RUz in the period of 2013-2016.

Methodology and Study Design: Genotyping assay of polymorphism of the genes under study was accomplished by the standard polymerase chain reaction (PCR). Peripheral blood of 107 patients with diagnosis chronic viral hepatitis C included in the main group and 81 relatively healthy donors (test group) was used for the molecular and genetic study of CYP2Е1*1В and CYP2C9*2 polymorphisms.

Results: Comparative analysis revealed differences in the distribution of allele frequencies of polymorphisms 430C > T CYP2C9 gene and gene C9896G CYP2E1 * 1B in groups of patients with chronic HCV group and population control. In the main group of patients with chronic HCV mutant allele "T » CYP2C9 gene met significantly more frequently in comparison with the control group population. Thus, the highest frequency of the mutant allele of the "T", as compared with the control group was observed in patients with moderate HCV activity. This is the lowest frequency of this genotype was observed in the subgroup of patients with liver cirrhosis. Our studies have shown that the accumulation of the mutant allele «G» CYP2E1 * 1B gene was also the case in almost all sub-groups of patients with chronic HCV. The frequency of heterozygous genotype CYP2E1*1B polymorphism in the population control group was 13.6%. It should be noted that the highest frequency component of genotype C/G was detected in the group of patients with chronic HCV with high activity. The data obtained indicate an association genotype C/G with the activation process of inflammation and fibrotic changes.

Conclusion: The results showed a high frequency of mutant allele "T" polymorphism 430C > T CYP2C9 with HCV, which allows us to consider the CYP2C9 gene as a factor of a favorable outcome of chronic hepatitis C. The association between the expression of CYP2E1 * 1B and progression of the disease with activation fibrosis-formation in individuals of Uzbek population is an important factor in the development of personalized therapy.