TY  - CONF
AU  - Krajnović, Milena
AU  - Jovanović-Ćupić, Snežana
AU  - Kokanov, Nikola
AU  - Petrović, Nina
AU  - Kožik, Bojana
AU  - Šiljić, Marina
AU  - Ćirković, Valentina
PY  - 2024
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/13314
AB  - Variations in the hepatitis C virus (HCV) core gene are related to the progression of liver fibrosis and therapy response. However, the influence of individual amino acid (aa) substitutions at different positions of HCV Core protein on the response to combined pegylated interferon/ribavirin (PEG-IFN/RBV) therapy and disease progression is not yet fully understood. The HCV Core protein can inactivate various genes in the host genome by affecting the methylation of their promoters, leading to liver damage and carcinogenesis. Two genes whose methylation status is affected by the HCV Core protein are the tumor suppressor genes RASSF1A and p16. We have previously shown that the methylation status of these two genes, together with the single nucleotide polymorphism (SNP) rs12979860 near the interleukin-28 beta subunit (IL-28B) gene, influences the response to combined therapy. Herein, we investigated a possible association between detected aa substitutions in HCV Core protein and response to combined therapy, liver disease progression, IL28B genotype, and the methylation status of the RASSF1A and p16 genes. In 29 examined patients we found no association between individual aa substitutions and therapy response. However, we observed that patients with HCV Core aa substitutions at position 75 and CT/TT IL28B genotypes were non-responders (NR) (p=0.023), which was associated with the presence of unmethylated RASSF1A gene. In contrast, even 75% of patients with aa substitutions at position 91 and CC IL28B genotype achieved a sustained virologic response (SVR) (p=0.030), and 70% of them had methylated RASSF1A gene. There was no significant association between the methylation status of the p16 gene and aa variations in the HCV core region. Our results suggest that combined analysis of aa substitutions in HCV Core protein, IL28B genotype, and methylation status of the RASSF1A gene may help predict response to PEG-IFN/RBV therapy in patients with chronic hepatitis C genotype 1b.xx
C3  - Genetics & Applications
T1  - Sequence variability of HCV core region and host genetic and epigenetic factors can predict the response to combined PEG-IFN/RBV therapy in patients with chronic hepatitis c infection genotype 1B
SP  - 26
EP  - 26
UR  - https://hdl.handle.net/21.15107/rcub_vinar_13314
ER  - 

@conference{
author = "Krajnović, Milena and Jovanović-Ćupić, Snežana and Kokanov, Nikola and Petrović, Nina and Kožik, Bojana and Šiljić, Marina and Ćirković, Valentina",
year = "2024",
abstract = "Variations in the hepatitis C virus (HCV) core gene are related to the progression of liver fibrosis and therapy response. However, the influence of individual amino acid (aa) substitutions at different positions of HCV Core protein on the response to combined pegylated interferon/ribavirin (PEG-IFN/RBV) therapy and disease progression is not yet fully understood. The HCV Core protein can inactivate various genes in the host genome by affecting the methylation of their promoters, leading to liver damage and carcinogenesis. Two genes whose methylation status is affected by the HCV Core protein are the tumor suppressor genes RASSF1A and p16. We have previously shown that the methylation status of these two genes, together with the single nucleotide polymorphism (SNP) rs12979860 near the interleukin-28 beta subunit (IL-28B) gene, influences the response to combined therapy. Herein, we investigated a possible association between detected aa substitutions in HCV Core protein and response to combined therapy, liver disease progression, IL28B genotype, and the methylation status of the RASSF1A and p16 genes. In 29 examined patients we found no association between individual aa substitutions and therapy response. However, we observed that patients with HCV Core aa substitutions at position 75 and CT/TT IL28B genotypes were non-responders (NR) (p=0.023), which was associated with the presence of unmethylated RASSF1A gene. In contrast, even 75% of patients with aa substitutions at position 91 and CC IL28B genotype achieved a sustained virologic response (SVR) (p=0.030), and 70% of them had methylated RASSF1A gene. There was no significant association between the methylation status of the p16 gene and aa variations in the HCV core region. Our results suggest that combined analysis of aa substitutions in HCV Core protein, IL28B genotype, and methylation status of the RASSF1A gene may help predict response to PEG-IFN/RBV therapy in patients with chronic hepatitis C genotype 1b.xx",
journal = "Genetics & Applications",
title = "Sequence variability of HCV core region and host genetic and epigenetic factors can predict the response to combined PEG-IFN/RBV therapy in patients with chronic hepatitis c infection genotype 1B",
pages = "26-26",
url = "https://hdl.handle.net/21.15107/rcub_vinar_13314"
}

Krajnović, M., Jovanović-Ćupić, S., Kokanov, N., Petrović, N., Kožik, B., Šiljić, M.,& Ćirković, V.. (2024). Sequence variability of HCV core region and host genetic and epigenetic factors can predict the response to combined PEG-IFN/RBV therapy in patients with chronic hepatitis c infection genotype 1B. in Genetics & Applications, 26-26.
https://hdl.handle.net/21.15107/rcub_vinar_13314

Krajnović M, Jovanović-Ćupić S, Kokanov N, Petrović N, Kožik B, Šiljić M, Ćirković V. Sequence variability of HCV core region and host genetic and epigenetic factors can predict the response to combined PEG-IFN/RBV therapy in patients with chronic hepatitis c infection genotype 1B. in Genetics & Applications. 2024;:26-26.
https://hdl.handle.net/21.15107/rcub_vinar_13314 .

Krajnović, Milena, Jovanović-Ćupić, Snežana, Kokanov, Nikola, Petrović, Nina, Kožik, Bojana, Šiljić, Marina, Ćirković, Valentina, "Sequence variability of HCV core region and host genetic and epigenetic factors can predict the response to combined PEG-IFN/RBV therapy in patients with chronic hepatitis c infection genotype 1B" in Genetics & Applications (2024):26-26,
https://hdl.handle.net/21.15107/rcub_vinar_13314 .

TY  - JOUR
AU  - Kokanov, Nikola
AU  - Jovanović-Ćupić, Snežana
AU  - Šiljić, Marina
AU  - Ćirković, Valentina
AU  - Petrović, Nina
AU  - Kožik, Bojana
AU  - Krajnović, Milena
PY  - 2023
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/12051
AB  - Variations in the hepatitis C virus (HCV) core sequence have been related to disease progression and response to antiviral therapy. Previously we showed that the methylation status of RASSF1A and p16 genes, and IL28B genotypes affects the response to pegylated interferon/ribavirin (PEG-IFN/RBV) therapy. Herein we investigated whether amino acid (aa) substitutions in the HCV core region alone or in combination with IL28B genotypes and RASSF1A/p16 methylation affect the response to PEG-IFN/RBV therapy and liver disease progression. Among 29 examined patients, we found no association between single aa substitutions and response to therapy. However, we observed that patients with the HCV core aa substitution at position 75 and CT/TT IL28B genotypes were non-responders (NR), (P=0.023). Moreover, these patients had unmethylated RASSF1A. In contrast, most patients (75%) with aa substitutions at position 91 and CC IL28B genotype achieved sustained virologic response (SVR), (P=0.030), and 70% of them had methylated RASSF1A gene. Our results suggest that combined analysis of aa substitutions in the core protein, the IL28B rs12979860 polymorphism, and the methylation status of the RASSF1A gene may help in predicting treatment response to PEG-IFN/RBV in genotype 1b chronic hepatitis C patients.
T2  - Archives of Biological Sciences
T1  - Variability of the HCV core region and host genetic and epigenetic factors can predict the response to pegylated interferon/ribavirin therapy in genotype 1b hepatitis C patients from Serbia
VL  - 75
IS  - 3
SP  - 251
EP  - 262
DO  - 10.2298/ABS230316020K
ER  - 

@article{
author = "Kokanov, Nikola and Jovanović-Ćupić, Snežana and Šiljić, Marina and Ćirković, Valentina and Petrović, Nina and Kožik, Bojana and Krajnović, Milena",
year = "2023",
abstract = "Variations in the hepatitis C virus (HCV) core sequence have been related to disease progression and response to antiviral therapy. Previously we showed that the methylation status of RASSF1A and p16 genes, and IL28B genotypes affects the response to pegylated interferon/ribavirin (PEG-IFN/RBV) therapy. Herein we investigated whether amino acid (aa) substitutions in the HCV core region alone or in combination with IL28B genotypes and RASSF1A/p16 methylation affect the response to PEG-IFN/RBV therapy and liver disease progression. Among 29 examined patients, we found no association between single aa substitutions and response to therapy. However, we observed that patients with the HCV core aa substitution at position 75 and CT/TT IL28B genotypes were non-responders (NR), (P=0.023). Moreover, these patients had unmethylated RASSF1A. In contrast, most patients (75%) with aa substitutions at position 91 and CC IL28B genotype achieved sustained virologic response (SVR), (P=0.030), and 70% of them had methylated RASSF1A gene. Our results suggest that combined analysis of aa substitutions in the core protein, the IL28B rs12979860 polymorphism, and the methylation status of the RASSF1A gene may help in predicting treatment response to PEG-IFN/RBV in genotype 1b chronic hepatitis C patients.",
journal = "Archives of Biological Sciences",
title = "Variability of the HCV core region and host genetic and epigenetic factors can predict the response to pegylated interferon/ribavirin therapy in genotype 1b hepatitis C patients from Serbia",
volume = "75",
number = "3",
pages = "251-262",
doi = "10.2298/ABS230316020K"
}

Kokanov, N., Jovanović-Ćupić, S., Šiljić, M., Ćirković, V., Petrović, N., Kožik, B.,& Krajnović, M.. (2023). Variability of the HCV core region and host genetic and epigenetic factors can predict the response to pegylated interferon/ribavirin therapy in genotype 1b hepatitis C patients from Serbia. in Archives of Biological Sciences, 75(3), 251-262.
https://doi.org/10.2298/ABS230316020K

Kokanov N, Jovanović-Ćupić S, Šiljić M, Ćirković V, Petrović N, Kožik B, Krajnović M. Variability of the HCV core region and host genetic and epigenetic factors can predict the response to pegylated interferon/ribavirin therapy in genotype 1b hepatitis C patients from Serbia. in Archives of Biological Sciences. 2023;75(3):251-262.
doi:10.2298/ABS230316020K .

Kokanov, Nikola, Jovanović-Ćupić, Snežana, Šiljić, Marina, Ćirković, Valentina, Petrović, Nina, Kožik, Bojana, Krajnović, Milena, "Variability of the HCV core region and host genetic and epigenetic factors can predict the response to pegylated interferon/ribavirin therapy in genotype 1b hepatitis C patients from Serbia" in Archives of Biological Sciences, 75, no. 3 (2023):251-262,
https://doi.org/10.2298/ABS230316020K . .