Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019163 (hepatitis B)
 38,309 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A complementary DNA library was constructed from mRNA of rat liver induced by an initiating dose of a chemical carcinogen, diethylnitrosamine. Using a differential hybridization technique, a complementary DNA clone which is induced more than 10-fold by an acute single dose of diethylnitrosamine was identified. The DNA sequence of this clone was matched with rat microsomal epoxide hydrolase. This gene may be of great interest, since it was found to be highly expressed in neoplastic nodules and primary hepatocellular carcinomas induced by different carcinogenic regimes. The inducible high level expression of this gene becomes constitutive during the process of hepatocarcinogenesis. The gene was also found to be inducibly expressed during partial hepatectomy in a similar manner as a multidrug-resistant gene (mdr-I). No change in the transcriptional initiation site was observed in the gene expression between induced and uninduced rat livers. The 5' upstream region of the gene was characterized and some potential controlling elements for gene regulation, such as Sp-1, AP-2, and Hepatitis B virus enhancer, were found. Based on our own and published results, we hypothesize that the altered expression of this xenobiotic enzyme in nodules and cancer cells could be a result of constitutive internal stimuli which might be associated with cell growth.
 ...
PMID:Expression of rat microsomal epoxide hydrolase gene during liver chemical carcinogenesis. 240 Sep 88

Hepatocellular carcinoma (HCC) is the fourth most common cancer worldwide, the main etiological factors being chronic infections with hepatitis B and C viruses. Genetic polymorphic forms of glutathione-S-transferase (GST) and microsomal epoxide hydrolase (mEPHX) have been associated with risk for various malignancies. The present study was undertaken to evaluate the association of GSTT1 and GSTM1 null genotypes and mEPHX polymorphisms with hepatitis virus-related HCC risk in an Indian population. Three groups of subjects were considered, control (n = 169), chronic viral hepatitis (n = 174), and HCC (n = 63). Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used for this polymorphic study. Genotype distributions between categories were compared using the chi2 test; odds ratios (ORs) and 95% confidence interval were calculated to express the relative risk. GSTT1 null genotype was associated with 2.23-fold (p < 0.05) increased risk for HCC development as compared to the control group. However, GSTM1 null genotype was found to have a protective effect when hepatitis patients were considered. In case of mEPHX, R139R imposed a risk factor for HCC with both control (OR = 1.81) and chronic hepatitis-infected (OR = 2.06) subjects. Combination of heterozygous mutant genotypes at mEPHX exons 3 and 4 revealed a twofold risk (nonsignificant) for HCC. Further, combination of GSTM1 and T1 genotypes with either of exon 3 or 4 polymorphism of mEPHX displayed synergistic associations (risk or protective) for HCC development. GST and mEPHX variants share a positive association with viral-related HCC risk in Indian population, although a larger sample size is still required to confirm the results.
 ...
PMID:Glutathione-S-transferase and microsomal epoxide hydrolase polymorphism and viral-related hepatocellular carcinoma risk in India. 1881 71

1. A genome-wide in silico screening rendered the genes of phase II enzymes in the rat genome whose promoters contain the putative DNA elements interacting with CCAAT/enhancer binding protein (C/EBP) and NF-E2-related factor (Nrf2). The hepatitis B virus X (HBx) protein strongly modulates the transactivation and/or the repression of genes regulated by some bZIP transcription factors. 2. This study investigated the effects of HBx on the induction of phase II enzymes with the aim of elucidating the role of HBx interaction with C/EBPbeta or Nrf2 bZIP transcription factors in hepatocyte-derived cells. 3. Immunoblot and reporter gene analyses revealed that transfection of HBx interfered with the constitutive and inducible GSTA2 transactivation promoted by oltipraz (C/EBPbeta activator), but not that by tert-butylhydroquinone (t-BHQ, Nrf2 activator). Moreover, HBx transfection completely inhibited GSTA2 reporter gene activity induced by C/EBPbeta, but failed to inhibit that by Nrf2. 4. Gel shift assays identified that HBx inhibited the increase in C/EBPbeta-DNA complex formation by oltipraz, but not the increase in Nrf2-DNA complex by t-BHQ. Immunoprecipitation and immunoblot assays verified the direct interaction between HBx and C/EBPbeta. Moreover, chromatin immunoprecipitation assays confirmed HBx inhibition of C/EBPbeta binding to its binding site in the GSTA2 gene promoter. HBx repressed the induction of other phase II enzymes including GSTP, UDP-glucuronyltransferase 1A, microsomal epoxide hydrolase, GSTM1, GSTM2, and gamma-glutamylcysteine synthase. 5. These results demonstrate that HBx inhibits the induction of phase II detoxifying enzymes, which is mediated by its interaction with C/EBPbeta, but not Nrf2, substantiating the specific role of HBx in phase II detoxifying capacity.
 ...
PMID:Role of hepatitis B virus X repression of C/EBPbeta activity in the down-regulation of glutathione S-transferase A2 gene: implications in other phase II detoxifying enzyme expression. 1925 44

Hepatocellular carcinoma (HCC) is a life-threatening disease that is often associated with chronic infection by hepatitis B and C viruses. Genetic polymorphisms have been reported to alter the risk for HCC development. Genetic studies based on the haplotype have an increased power for detecting disease associations compared with single-nucleotide polymorphism-based analysis. There is sufficient epidemiological evidence suggesting a link between genetic polymorphism and haplotypes of microsomal epoxide hydrolase (mEPHX) and X-ray cross-complementing group 1 (XRCC1) with altered cancer risk. However, no report correlates the risk of HCC development with mEPHX and XRCC1 haplotypes. Genetic polymorphism of these genes was studied for haplotype construction in 169 control subjects, 174 hepatitis patients, and 63 HCC patients. 113Tyr-139Arg and 113His-139His haplotypes of mEPHX significantly elevated the risk for HCC by 1.4- and 1.5-folds, respectively. Arg-His-Arg haplotype of XRCC1 significantly enhanced the risk for hepatitis by 2.8-folds (p = 0.001), but not for HCC (odds ratio = 1.5; p = 0.28). mEPHX haplotypes shared a positive association with HCC risk in India.
 ...
PMID:Haplotypes of microsomal epoxide hydrolase and x-ray cross-complementing group 1 genes in Indian hepatocellular carcinoma patients. 1975 50

To clarify the association between microsomal epoxide hydrolase gene (EPHX1) Tyr113His polymorphism and hepatocellular carcinoma (HCC) risk, a meta-analysis was performed. Overall, EPHX1 Tyr113His polymorphism was associated with increased risk of HCC. Subgroup analyses by status of Hardy-Weinberg equilibrium (HWE) in controls further confirmed this association. Through a literature search, 119 relevant records were identified, and 17 individual case-control studies from 13 publications were finally included, involving a total of 1,480 HCC cases and 2,564 controls. In subgroup analyses, increased associations were found in Asians, Caucasians, hepatitis B virus (HBV)- dominant areas, hepatitis C virus (HCV)-dominant areas, high-rate areas of HCC, and medium-rate areas of HCC, but not in Africans and low-rate areas of HCC, respectively. This meta-analysis suggests that EPHX1 Tyr113His polymorphism contributes to HCC risk.
 ...
PMID:[EPHX1 Tyr113His polymorphism contributes to hepatocellular carcinoma risk: evidfnce from a meta-analysis]. 2606 63