Liver Cirrhosis in Chronic Hepatitis B Patients Is Associated with Genetic Variations in DNA Repair Pathway Genes
Liver cirrhosis (LC), contributing to more than 1 million of deaths annually, is a major healthcare concern worldwide. Hepatitis B virus (HBV) is a major LC etiological factor, and 15% of patients with chronic HBV infection (CHB) develop LC within 5 years. Recently, novel host genetic determinants w...
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MDPI AG
2020-11-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/12/11/3295 |
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| author | Magda Rybicka Anna Woziwodzka Alicja Sznarkowska Tomasz Romanowski Piotr Stalke Marcin Dręczewski Eloi R. Verrier Thomas F. Baumert Krzysztof Piotr Bielawski |
| author_facet | Magda Rybicka Anna Woziwodzka Alicja Sznarkowska Tomasz Romanowski Piotr Stalke Marcin Dręczewski Eloi R. Verrier Thomas F. Baumert Krzysztof Piotr Bielawski |
| author_sort | Magda Rybicka |
| collection | DOAJ |
| description | Liver cirrhosis (LC), contributing to more than 1 million of deaths annually, is a major healthcare concern worldwide. Hepatitis B virus (HBV) is a major LC etiological factor, and 15% of patients with chronic HBV infection (CHB) develop LC within 5 years. Recently, novel host genetic determinants were shown to influence HBV lifecycle and CHB course. DNA repair enzymes can affect dynamics of liver damage and are involved in HBV covalently closed circular DNA (cccDNA) formation, an essential step for viral replication. This study aimed to evaluate the possible role of genes representing key DNA-repair pathways in HBV-induced liver damage. MALDI-TOF MS genotyping platform was applied to evaluate variations within <i>XRCC1</i>, <i>XRCC4</i>, <i>ERCC2</i>, <i>ERCC5</i>, <i>RAD52</i>, <i>Mre11</i>, and <i>NBN</i> genes. Apart from older age (<i>p</i> < 0.001), female sex (<i>p</i> = 0.021), portal hypertension (<i>p</i> < 0.001), thrombocytopenia (<i>p</i> < 0.001), high HBV DNA (<i>p</i> = 0.001), and high aspartate aminotransferase (AST) (<i>p</i> < 0.001), we found that G allele at rs238406 (<i>ERCC2</i>, <i>p</i> = 0.025), T allele at rs25487 (<i>XRCC1</i>, <i>p</i> = 0.012), rs13181 GG genotype (<i>ERCC2</i>, <i>p</i> = 0.034), and C allele at rs2735383 (<i>NBN</i>, <i>p</i> = 0.042) were also LC risk factors. The multivariate logistic regression model showed that rs25487 CC (<i>p</i> = 0.005) and rs238406 TT (<i>p</i> = 0.027) were independently associated with lower risk of LC. This study provides evidence for the impact of functional and potentially functional variations in key DNA-repair genes <i>XRCC1</i> and <i>ERCC2</i> in HBV-induced liver damage in a Caucasian population. |
| first_indexed | 2024-03-10T15:02:03Z |
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| last_indexed | 2024-03-10T15:02:03Z |
| publishDate | 2020-11-01 |
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| spelling | doaj.art-533dc251c6ef4e7f8a8ee6045ad2496e2023-11-20T20:07:43ZengMDPI AGCancers2072-66942020-11-011211329510.3390/cancers12113295Liver Cirrhosis in Chronic Hepatitis B Patients Is Associated with Genetic Variations in DNA Repair Pathway GenesMagda Rybicka0Anna Woziwodzka1Alicja Sznarkowska2Tomasz Romanowski3Piotr Stalke4Marcin Dręczewski5Eloi R. Verrier6Thomas F. Baumert7Krzysztof Piotr Bielawski8Department of Molecular Diagnostics, Intercollegiate Faculty of Biotechnology, University of Gdansk and Medical University of Gdansk, Abrahama 58, 80-307 Gdansk, PolandDepartment of Molecular Diagnostics, Intercollegiate Faculty of Biotechnology, University of Gdansk and Medical University of Gdansk, Abrahama 58, 80-307 Gdansk, PolandDepartment of Molecular Diagnostics, Intercollegiate Faculty of Biotechnology, University of Gdansk and Medical University of Gdansk, Abrahama 58, 80-307 Gdansk, PolandDepartment of Molecular Diagnostics, Intercollegiate Faculty of Biotechnology, University of Gdansk and Medical University of Gdansk, Abrahama 58, 80-307 Gdansk, PolandDepartment of Infectious Diseases, Medical University of Gdansk, ul. Powstania Styczniowego 9b, 81-519 Gdynia, PolandDepartment of Infectious Diseases, Medical University of Gdansk, ul. Powstania Styczniowego 9b, 81-519 Gdynia, PolandInserm, Institut de Recherche sur les Maladies Virales et Hépatiques UMR_S1110, Université de Strasbourg, F-67000 Strasbourg, FranceInserm, Institut de Recherche sur les Maladies Virales et Hépatiques UMR_S1110, Université de Strasbourg, F-67000 Strasbourg, FranceDepartment of Molecular Diagnostics, Intercollegiate Faculty of Biotechnology, University of Gdansk and Medical University of Gdansk, Abrahama 58, 80-307 Gdansk, PolandLiver cirrhosis (LC), contributing to more than 1 million of deaths annually, is a major healthcare concern worldwide. Hepatitis B virus (HBV) is a major LC etiological factor, and 15% of patients with chronic HBV infection (CHB) develop LC within 5 years. Recently, novel host genetic determinants were shown to influence HBV lifecycle and CHB course. DNA repair enzymes can affect dynamics of liver damage and are involved in HBV covalently closed circular DNA (cccDNA) formation, an essential step for viral replication. This study aimed to evaluate the possible role of genes representing key DNA-repair pathways in HBV-induced liver damage. MALDI-TOF MS genotyping platform was applied to evaluate variations within <i>XRCC1</i>, <i>XRCC4</i>, <i>ERCC2</i>, <i>ERCC5</i>, <i>RAD52</i>, <i>Mre11</i>, and <i>NBN</i> genes. Apart from older age (<i>p</i> < 0.001), female sex (<i>p</i> = 0.021), portal hypertension (<i>p</i> < 0.001), thrombocytopenia (<i>p</i> < 0.001), high HBV DNA (<i>p</i> = 0.001), and high aspartate aminotransferase (AST) (<i>p</i> < 0.001), we found that G allele at rs238406 (<i>ERCC2</i>, <i>p</i> = 0.025), T allele at rs25487 (<i>XRCC1</i>, <i>p</i> = 0.012), rs13181 GG genotype (<i>ERCC2</i>, <i>p</i> = 0.034), and C allele at rs2735383 (<i>NBN</i>, <i>p</i> = 0.042) were also LC risk factors. The multivariate logistic regression model showed that rs25487 CC (<i>p</i> = 0.005) and rs238406 TT (<i>p</i> = 0.027) were independently associated with lower risk of LC. This study provides evidence for the impact of functional and potentially functional variations in key DNA-repair genes <i>XRCC1</i> and <i>ERCC2</i> in HBV-induced liver damage in a Caucasian population.https://www.mdpi.com/2072-6694/12/11/3295HBVliver cirrhosisgenetic polymorphismDNA repair<i>XRCC1</i><i>ERCC2</i> |
| spellingShingle | Magda Rybicka Anna Woziwodzka Alicja Sznarkowska Tomasz Romanowski Piotr Stalke Marcin Dręczewski Eloi R. Verrier Thomas F. Baumert Krzysztof Piotr Bielawski Liver Cirrhosis in Chronic Hepatitis B Patients Is Associated with Genetic Variations in DNA Repair Pathway Genes Cancers HBV liver cirrhosis genetic polymorphism DNA repair <i>XRCC1</i> <i>ERCC2</i> |
| title | Liver Cirrhosis in Chronic Hepatitis B Patients Is Associated with Genetic Variations in DNA Repair Pathway Genes |
| title_full | Liver Cirrhosis in Chronic Hepatitis B Patients Is Associated with Genetic Variations in DNA Repair Pathway Genes |
| title_fullStr | Liver Cirrhosis in Chronic Hepatitis B Patients Is Associated with Genetic Variations in DNA Repair Pathway Genes |
| title_full_unstemmed | Liver Cirrhosis in Chronic Hepatitis B Patients Is Associated with Genetic Variations in DNA Repair Pathway Genes |
| title_short | Liver Cirrhosis in Chronic Hepatitis B Patients Is Associated with Genetic Variations in DNA Repair Pathway Genes |
| title_sort | liver cirrhosis in chronic hepatitis b patients is associated with genetic variations in dna repair pathway genes |
| topic | HBV liver cirrhosis genetic polymorphism DNA repair <i>XRCC1</i> <i>ERCC2</i> |
| url | https://www.mdpi.com/2072-6694/12/11/3295 |
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