Introduction. The present research explores data and analyzes molecular mechanisms appraisal of the clinical course of chronic viral hepatitis C, registered considering the prognostic significance of the CYP2C9 isoenzyme. The aim of the research is to assess the molecular mechanisms of the clinical course of CVHC, considering the prognostic significance of the CYP2C9 isoenzyme, responsible for the xenobiotic biotransformation system, in representatives of the Uzbek population. Materials and methods. 107 patients with chronic viral hepatitis C (CVHC) were involved in the research group, further were divided into three subgroups to assess the association of polymorphic markers of the СУР2С9 genes. The criteria for inclusion in the research were clinical, biochemical and instrumental verification of the diagnosis with the determination of both the stage and severity of the disease, as well as the detection of hepatitis C virus RNA by the AmpliSens® HCV-FRT test system detected by polymerase chain reaction (PCR) on a RotorGene 6000 instrument. Results and discussion. Research data determined that a relationship was established between the mutant allele of CYP2C9 gene polymorphism with more favorable course of CVHC. This assumption is also confirmed by the reduced frequency of the mutant allele in the subgroup of patients with highly active CVHC, which may indicate the protective role of this allele in activating the inflammatory process in CVHC. It was revealed that a high level of theoretically expected heterozygosity is the indicator of genetic diversity in the subgroup of patients with high active CVHC. Conclusion. The results of the research suggest that CYP2C9 gene polymorphism can be considered as a conditionally “protective” marker for disease progression and requires further study in a larger sample of patients.
1. Islambekova Z.A. Reducing the prevalence of viral hepatitis B and C in Uzbekistan - a component for the prevention of hepatocellular carcinoma // Oncology. - 2009. - T. 11, No. 2. - P. 154-157 (in Russian). 2. Perz J., Armstrong G., Farrington L. et al. The contribution of hepatitis B and hepatitis C viral infections to cirrhosis and primary liver cancer worldwide. // J. Hepatol., 2006.-№45:- Р.529-538. 3. Bosch F.X.,Ribes J., Cleries R. et al. Epidemiology of hepatocellular carcinoma// Clin Liver Dis.–2005. – Vol. 9, №2. – Р. 191-211. 4. Shepard C.W., Finelli L., Alter M.J. Global epidemiology of hepatitis C virus infection.// Lancet Infect Dis .-2005.-№5.-Р.558-567. 5. Pilotto A., Seripa D., Franceschi M. et al. Genetic susceptibility to nonsteroidal anti-inflammatory drug-related gastroduodenal bleeding: role of cytochrome P450 2C9 polymorphisms.// Gastroenterology.-2007.- №133.- Р.465-471. 6. Aynacioglu A.S., Brockmoller J., Bauer S., et al. Frequency of cytochrome P450 CYP2C9 variants in a Turkish population and functional relevance for phenytoin // Br. J. Clin. Pharmacol. –1999. –Vol. 483. –P.409-415. 7. Seng K.C., Gin G.G., Sangkar J.V., Phipps M.E. Frequency of Cytochrome P450 2C9 (CYP2C9) Alleles in Three Ethnic Groups in Malaysia // Asia Pacific J. of Mol. Biol. and Biotech. –2003. –Vоl 1. –P.83-91. 8. Bae J.-W., Kim H.-K., Kim J.-H. et al. Allele and genotype frequencies of CYP2C9 in a Korean population // Br. J. Clin. Pharmacol. –2005. –Vol. 60. – Р.418–422. 9. Sychev D.A., Stasyak E.V., Ignatiev I.V. et al. Clinical pharmacogenetics of the isoenzyme of cytochrome P-450 2C9 // Klin.pharmacol. and ter. - 2005.- No. 4.- P.60–63 (in russian). 10. Blackard J. N., Shire N.J. et al. Acute hepatitis C virus infection:a chronic problem//Hepatology.- 2008.– Vol. 47. – Р. 321-331 11. Albeldawi et al. Hepatitis C virus: prevention, screening, and interpretation of assays. ClevelClin// J. Med.– 2010. – Vol. 77. – Р. 16–26. 12. Gochee P.A., Jonsson J.R., Clouston A.D., et al. Steatosis in chronic hepatitis C: association with increased messenger RNA expression of сollagen I, tumor necrosis factor-alpha and cytochrome P450 2E1 // J Gastroenterol Hepatol. –2003, Apr. –18(4). –Р.386-392. 13. Frye R.F.,Zgheib N.K.,Matzke G.R., et al. Liver disease selectively modulates cytochrome P450--mediated metabolism // Clin Pharmacol Ther.–2006 Sep.– Vol.80, №3. –Р.235-245. 14. Carlquist J., Horne B., Muhlestein J. at al. Genotypes of the cytochrome p450 isoform, CYP2C9, and the vitamin K epoxide reductase complex subunit 1 conjointly determine stable warfarin dose: a prospective study // Journal of Thrombosis and Thrombolysis. – 2006. – Vol. 22. –Р.191-197.
Azimova, Sevara B.; Talipova, Naila K.; and Nurmukhamedova, Nozima S.
"PRINCIPAL ASPECTS OF PATHOGENESIS OF CHRONIC VIRAL HEPATITIS IN UZBEKISTAN,"
Central Asian Journal of Medicine: Vol. 2020
, Article 15.
Available at: https://uzjournals.edu.uz/tma/vol2020/iss1/15