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Vitamin D receptor ApaI polymorphism associated with progression of liver disease in Vietnamese patients chronically infected with hepatitis B virus.

ABSTRACT: BACKGROUND:Vitamin D derivatives and their receptor (VDR) are potent modulators of immune responses in various diseases including malignancies as well as in metabolic and infectious disorders. The impact of vitamin D receptor polymorphisms on clinical outcomes of hepatitis B virus (HBV) infection is not well understood. This study aims to investigate the potential role of VDR polymorphisms (TaqI, FokI, ApaI, and BsmI) in Vietnamese HBV infected patients and to correlate these polymorphisms with the progression of HBV-related liver disease. METHODS:Four hundred forty-three HBV infected patients of the three clinically well-defined subgroups chronic hepatitis B (CHB, n =?183), liver cirrhosis (LC, n =?89) and hepatocellular carcinoma (HCC, n =?171) and 238 healthy individuals (HC) were enrolled. VDR polymorphisms were genotyped by DNA sequencing and in-house validated ARMS assays. Logistic regression models were applied in order to determine the association of VDR polymorphisms with manifest HBV infection as well as with progression of related liver diseases mulin different genetic models. RESULTS:The VDR ApaI CA genotype was less frequent in HCC than in CHB patients in different genetic models (codominant model, OR?=?0.5, 95%CI?=?0.3-0.84, P =?0.004; dominant model, OR?=?0.46, 95%CI?=?0.27-0.76, P =?0.0023). In the recessive model, the genotype ApaI AA was found more frequently among HCC compared to CHB patients (OR?=?2.56, 95%CI?=?1.01-6.48, P =?0.04). Similarly, the ApaI CA genotype was less frequent in HCC than in non-HCC group codominant model, OR?=?0.6, 95%CI?=?0.4-0.98, dominant model, P =?0.04 and OR?=?0.6, 95%CI?=?0.38-0.90, P =?0.017). The ApaI genotypes CA and AA was significantly associated with higher levels of liver enzymes, bilirubin, and HBV DNA (P

SUBMITTER: Hoan NX

PROVIDER: S-EPMC6925483 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Vitamin D receptor ApaI polymorphism associated with progression of liver disease in Vietnamese patients chronically infected with hepatitis B virus.

Hoan Nghiem Xuan NX Khuyen Nguyen N Giang Dao Phuong DP Binh Mai Thanh MT Toan Nguyen Linh NL Anh Do Tuan DT Trung Ngo Tat NT Bang Mai Hong MH Meyer Christian G CG Velavan Thirumalaisamy P TP Song Le Huu LH

BMC medical genetics 20191221 1

<h4>Background</h4>Vitamin D derivatives and their receptor (VDR) are potent modulators of immune responses in various diseases including malignancies as well as in metabolic and infectious disorders. The impact of vitamin D receptor polymorphisms on clinical outcomes of hepatitis B virus (HBV) infection is not well understood. This study aims to investigate the potential role of VDR polymorphisms (TaqI, FokI, ApaI, and BsmI) in Vietnamese HBV infected patients and to correlate these polymorphis ...[more]

PMID: 31864292

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Project description:Cirrhosis derived from chronic hepatitis C virus (HCV) infection is still a common indication for liver transplantation (LT). Reinfection of the engrafted liver is universal in patients with detectable viral RNA at the time of transplant and causes fast progression of cirrhosis (within 5 years) in around one-third of these patients. To prevent damage to the liver graft, effective direct-acting antiviral (DAA) therapy is required as soon as possible. However, because of post-LT clinical instability, it is difficult to determine the optimal time to start DAAs with a low risk of complications. Evaluate changes in quasispecies complexity following LT and seek a predictive index of fast liver damage progression to determine the timing of DAA initiation. HCV genomes isolated from pre-LT and 15-day post-LT serum samples of ten patients, who underwent orthotopic LT, were quantified and sequenced using a next-generation sequencing platform. Sequence alignments, phylogenetic trees, quasispecies complexity measures, biostatistics analyses, adjusted R2 values, and analysis of variance (ANOVA) were carried out. Three different patterns of reinfection were observed (viral bottlenecking, conserved pre-LT population, and mixed populations), suggesting that bottlenecking or homogenization of the viral population is not a generalized effect after liver graft reinfection. None of the quasispecies complexity measures predicted the future degree of liver damage. Higher and more uniform viral load (VL) values were observed in all pre-LT samples, but values were more dispersed in post-LT samples. However, VL increased significantly from the pre-LT to 15-day post-LT samples in patients with advanced fibrosis at 1-year post-LT, suggesting that a VL increase on day 15 may be a predictor of fast liver fibrosis progression. HCV kinetics after LT differ between patients and are not fibrosis-dependent. Higher VL at day 15 post-LT versus pre-LT samples may predict fast liver fibrosis progression.

Project description:Covalently closed circular DNA (cccDNA) forms the basis for replication and persistence of hepatitis B virus (HBV) in the chronically infected liver. We have previously shown that viral transcription is subject to regulation by posttranslational modifications (PTMs) of histone proteins bound to cccDNA through analysis of de novo HBV-infected cell lines. We now report the successful adaptation of this chromatin immunoprecipitation sequencing (ChIPseq) approach for analysis of fine-needle patient liver biopsy specimens to investigate the role of histone PTMs in chronically HBV-infected patients. Using 18 specimens from patients in different stages of chronic HBV infection, our work shows that the profile of histone PTMs in chronic infection is more nuanced than previously observed in in vitro models of acute infection. In line with our previous findings, we find that the majority of HBV-derived sequences are associated with the activating histone PTM H3K4me3. However, we show a striking interpatient variability of its deposition in this patient cohort correlated with viral transcription and patient HBV early antigen (HBeAg) status. Unexpectedly, we detected deposition of the classical inhibitory histone PTM H3K9me3 on HBV-DNA in around half of the patient biopsy specimens, which could not be linked to reduced levels of viral transcripts. Our results show that current in vitro models are unable to fully recapitulate the complex epigenetic landscape of chronic HBV infection observed in vivo and demonstrate that fine-needle liver biopsy specimens can provide sufficient material to further investigate the interaction of viral and host proteins on HBV-DNA.IMPORTANCE Hepatitis B virus (HBV) is a major global health concern, chronically infecting millions of patients and contributing to a rising burden of liver disease. The viral genome forms the basis for chronic infection and has been shown to be subject to regulation by epigenetic mechanisms, such as posttranslational modification of histone proteins. Here, we confirm and expand on previous results by adapting a high-resolution technique for analysis of histone modifications for use with patient-derived fine-needle liver biopsy specimens. Our work highlights that the situation in vivo is more complex than predicted by current in vitro models, for example, by suggesting a novel, noncanonical role of the histone modification H3K9me3 in the HBV life cycle. Importantly, enabling the use of fine-needle liver biopsy specimens for such high-resolution analyses may facilitate further research into the epigenetic regulation of the HBV genome.

Dataset Information

Vitamin D receptor ApaI polymorphism associated with progression of liver disease in Vietnamese patients chronically infected with hepatitis B virus.

Publications

Vitamin D receptor ApaI polymorphism associated with progression of liver disease in Vietnamese patients chronically infected with hepatitis B virus.

Similar Datasets

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