Liver Cirrhosis in Chronic Hepatitis B Patients Is Associated with Genetic Variations in DNA Repair Pathway Genes.
Fiche publication
Date publication
novembre 2020
Journal
Cancers
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BAUMERT Thomas, Dr VERRIER Eloi
Tous les auteurs :
Rybicka M, Woziwodzka A, Sznarkowska A, Romanowski T, Stalke P, Dręczewski M, Verrier ER, Baumert TF, Bielawski KP
Lien Pubmed
Résumé
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 , , , , , , and genes. Apart from older age ( < 0.001), female sex ( = 0.021), portal hypertension ( < 0.001), thrombocytopenia ( < 0.001), high HBV DNA ( = 0.001), and high aspartate aminotransferase (AST) ( < 0.001), we found that G allele at rs238406 (, = 0.025), T allele at rs25487 (, = 0.012), rs13181 GG genotype (, = 0.034), and C allele at rs2735383 (, = 0.042) were also LC risk factors. The multivariate logistic regression model showed that rs25487 CC ( = 0.005) and rs238406 TT ( = 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 and in HBV-induced liver damage in a Caucasian population.
Mots clés
DNA repair, ERCC2, HBV, XRCC1, genetic polymorphism, liver cirrhosis
Référence
Cancers (Basel). 2020 Nov 7;12(11):