ABSTRACT
@#Nonalcoholic fatty liver disease(NAFLD)as the most common hepatic disease worldwide is affected not only by extrinsic factors, but also by genetic ones. Type 2 diabetes mellitus(T2DM), another chronic disease regulated by both environmental and genetic factors, is closely related to NAFLD in signal pathways and susceptibility genes. This review summarizes the susceptibility genes of NAFLD, especially points out their relevance to T2DM and suggests their related clinical applications, which provide further evidence for the exploration of the mechanisms of the two diseases with a new direction for their diagnosis and treatment.
ABSTRACT
Herpes simplex virus type 1 encodes three sets of genes, α, ß, and γ, whose expression is sequentially ordered in a cascade fashion. The transactivators of α genes comprise virion protein 16 (VP16) and the cellular proteins octamer binding protein 1 (Oct1) and host factor 1 (HCF1). Efficient transition from α to ß gene expression requires the α protein ICP0 (infected cell protein 0). Earlier studies have shown that this protein binds to CoREST and displaces HDAC1 from the CoREST/REST/lysine-specific demethylase 1 (LSD1) repressor complex. Ultimately, the components of the repressor complex are translocated at least in part into the cytoplasm. A key event in activation of α genes is the recruitment of LSD1 to demethylate histones bound to the α gene promoters. LSD1 is unstable in the absence of its partner, CoREST, and raises the question of whether both CoREST and REST are involved in the initiation of transcription of the α genes. Here we show that CoREST or REST small interfering RNAs (siRNAs) destabilize CoREST, REST, LSD1, and Sin3A, another component of the repressor complex. In cells transfected with REST or CoREST siRNA, the accumulation of α proteins and mRNAs is delayed in comparison to those of mock-transfected or control siRNA-transfected cells. The LSD1/CoREST/REST compressor complex is thus sequentially necessary and subsequently inimical for viral gene expression.
Subject(s)
Gene Expression Regulation, Viral , Herpes Simplex/metabolism , Herpesvirus 1, Human/genetics , Nerve Tissue Proteins/metabolism , Repressor Proteins/metabolism , Cell Line, Tumor , Co-Repressor Proteins , Herpes Simplex/genetics , Herpes Simplex/virology , Herpesvirus 1, Human/metabolism , Humans , Nerve Tissue Proteins/genetics , Repressor Proteins/genetics , Viral Proteins/genetics , Viral Proteins/metabolismABSTRACT
<p><b>OBJECTIVE</b>To explore whether the TNFA promoter single nucleotide polymorphisms (SNPs) are associated with the outcomes of hepatitis B virus(HBV) infection in Chinese Han population.</p><p><b>METHODS</b>One hundred and forty-eight self-limited HBV infection subjects and 207 chronic hepatitis B patients were recruited. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and sequence specific primer-PCR(PCR-SSP) were used to detect the SNPs of five sites in TNFA promoter (-238G/A, -308G/A, -857C/T, -863C/A, -1031T/C). The frequency distributions of genotypes and haplotypes in different groups were analyzed by EPI and EH programs.</p><p><b>RESULTS</b>The frequencies of -238GG genotype in chronic hepatitis B patients were significantly higher than that in self-limited infection subjects (P=0.02). The frequencies of -857TT genotype in chronic hepatitis B patients were clearly lower than that in self-limited infection subjects (P=0.02). Haplotypic frequencies of GGCCT (-238/-308/-857/-863/-1031) in chronic hepatitis B patients was significantly lower than that in self-limited infection subjects (P=0.03), and the frequencies of haplotype GGCAT or GGTAT in chronic hepatitis B patients were clearly higher than those in self-limited infection subjects (P=0.0001; P=0.004).</p><p><b>CONCLUSION</b>TNFA promoter polymorphisms are important host genetic factors affecting the outcomes of HBV infection.</p>