Liver Cirrhosis in Chronic Hepatitis B Patients Is Associated with Genetic Variations in DNA Repair Pathway Genes

SIMPLE SUMMARY: As DNA repair enzymes affect dynamics of liver damage and are involved in HBV viral replication, this study focused on the role of genetic variations within genes representing key DNA-repair pathways in HBV-induced liver cirrhosis. The obtained results have demonstrated that SNPs wit...

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Detalles Bibliográficos
Autores principales: Rybicka, Magda, Woziwodzka, Anna, Sznarkowska, Alicja, Romanowski, Tomasz, Stalke, Piotr, Dręczewski, Marcin, Verrier, Eloi R., Baumert, Thomas F., Bielawski, Krzysztof Piotr
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7694950/
https://www.ncbi.nlm.nih.gov/pubmed/33171788
http://dx.doi.org/10.3390/cancers12113295
Descripción
Sumario:SIMPLE SUMMARY: As DNA repair enzymes affect dynamics of liver damage and are involved in HBV viral replication, this study focused on the role of genetic variations within genes representing key DNA-repair pathways in HBV-induced liver cirrhosis. The obtained results have demonstrated that SNPs within XRCC1, ERCC2 genes may confer susceptibility to liver cirrhosis in chronic hepatitis B patients. ABSTRACT: 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 XRCC1, XRCC4, ERCC2, ERCC5, RAD52, Mre11, and NBN genes. Apart from older age (p < 0.001), female sex (p = 0.021), portal hypertension (p < 0.001), thrombocytopenia (p < 0.001), high HBV DNA (p = 0.001), and high aspartate aminotransferase (AST) (p < 0.001), we found that G allele at rs238406 (ERCC2, p = 0.025), T allele at rs25487 (XRCC1, p = 0.012), rs13181 GG genotype (ERCC2, p = 0.034), and C allele at rs2735383 (NBN, p = 0.042) were also LC risk factors. The multivariate logistic regression model showed that rs25487 CC (p = 0.005) and rs238406 TT (p = 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 XRCC1 and ERCC2 in HBV-induced liver damage in a Caucasian population.

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