Epigenetics: A Molecular Link Between Environmental Factors and Type 2 Diabetes

Department of Clinical Sciences, Lund University Diabetes Center, Lund University, Malmö, Sweden.
Diabetes (Impact Factor: 8.47). 12/2009; 58(12):2718-25. DOI: 10.2337/db09-1003
Source: PubMed
Download full-text


Available from: Charlotte Ling, Nov 11, 2014
1 Follower
  • Source
    • "Like any complex phenotype, the epigenetic control of gene expression activity can be influenced by both genetic and environmental factors. In fact, recent research showed that the impact of the environment can be acquired via the epigenome (Fraga et al., 2005; Wong et al., 2005; Poulsen et al., 2007; Szyf et al., 2008; Ling and Groop, 2009), a hot area in complex disease studies including cancer that draws active research. With the rapid development in epigenomic analysis using next-generation sequencing or array-based technologies, the newly emerging epigenetic epidemiology is serving as a bridge linking gene activity with environmental conditions. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Since the final decades of the last century, twin studies have made a remarkable contribution to the genetics of human complex traits and diseases. With the recent rapid development in modern biotechnology of high-throughput genetic and genomic analyses, twin modelling is expanding from analysis of diseases to molecular phenotypes in functional genomics especially in epigenetics, a thriving field of research that concerns the environmental regulation of gene expression through DNA methylation, histone modification, microRNA and long non-coding RNA expression, etc. The application of the twin method to molecular phenotypes offers new opportunities to study the genetic (nature) and environmental (nurture) contributions to epigenetic regulation of gene activity during developmental, ageing and disease processes. Besides the classical twin model, the case co-twin design using identical twins discordant for a trait or disease is becoming a popular and powerful design for epigenome-wide association study in linking environmental exposure to differential epigenetic regulation and to disease status while controlling for individual genetic make-up. It can be expected that novel uses of twin methods in epigenetic studies are going to help with efficiently unravelling the genetic and environmental basis of epigenomics in human complex diseases. © 2015. Published by The Company of Biologists Ltd.
    Journal of Experimental Biology 01/2015; 218(Pt 1):134-139. DOI:10.1242/jeb.107151 · 3.00 Impact Factor
  • Source
    • "Our studies have shown that in diabetes hyper methylation of the CpG sites at the regulatory region of DNA polymerase gamma affects its binding to the mtDNA, and this compromises the transcriptional activity resulting in decreased copy number [52]. Hyper acetylation of histone H4 at the insulin gene promoter influences glucose-induced insulin secretion [53]. Diabetic patients with nephropathy have altered DNA methylation at the key gene promoters compared to those without nephropathy [54]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Diabetic retinopathy remains one of the most debilitating chronic complications, but despite extensive research in the field, the exact mechanism(s) responsible for how retina is damaged in diabetes remains ambiguous. Many metabolic pathways have been implicated in its development, and genes associated with these pathways are altered. Diabetic environment also facilitates epigenetics modifications, which can alter the gene expression without permanent changes in DNA sequence. The role of epigenetics in diabetic retinopathy is now an emerging area, and recent work has shown that genes encoding mitochondrial superoxide dismutase (Sod2) and matrix metalloproteinase-9 (MMP-9) are epigenetically modified, activates of epigenetic modification enzymes, histone lysine demethylase 1 (LSD1), and DNA methyltransferase are increased, and the micro RNAs responsible for regulating nuclear transcriptional factor and VEGF are upregulated. With the growing evidence of epigenetic modifications in diabetic retinopathy, better understanding of these modifications has potential to identify novel targets to inhibit this devastating disease. Fortunately, the inhibitors and mimics targeted towards histone modification, DNA methylation, and miRNAs are now being tried for cancer and other chronic diseases, and better understanding of the role of epigenetics in diabetic retinopathy will open the door for their possible use in combating this blinding disease.
    10/2013; 2013:635284. DOI:10.1155/2013/635284
  • Source
    • "The changes in gene expression are regarded as epigenetic events because they are caused by DNA methylation and histone modifications but without any change in the nucleotide sequence. The importance of the DNA methylation is indicated by the demonstration that an aberrant DNA methylation in CpG islands is involved in some human diseases, such as autoimmune diseases and cancer (Ling, 2009; Jones and Baylin, 2002; Feinberg et al., 2006; Cheng et al., 2004a). Activation of oncogenes by a decrease in DNA methylation was proposed to have a role in carcinogenesis. "
    [Show abstract] [Hide abstract]
    ABSTRACT: IDO1 can be induced by interferon gamma (IFN-γ) in multiple cell types. We have earlier described that the DNA methyltransferase inhibitor zebularine also induces IDO1 in several rat cell clones. We now describe a synergistic induction of IDO1 expression by IFN-γ and zebularine. To elucidate the mechanism of the IDO1 induction we have studied the methylation status in the promoter region of the IDO1 gene from both human monocytic THP-1 cells and H1D2 rat colon cancer cells. Interestingly, the IDO1 promoter is hypermethylated and IFN-γ is shown to induce a significant demethylation. The synergism in effect of zebularine and IFN-γ on IDO1 expression is paralleled by a similar synergistic effect on expression of two other IFN-γ-responsive genes, the transcription factors STAT1 and IRF1 with binding sites in the IDO1 promoter region. The demonstrated synergistic activation of IDO1 expression has implications in relation to therapeutic induction of immunosuppression in autoimmunity and chronic inflammation.
    Molecular Immunology 03/2012; 51(2):101-11. DOI:10.1016/j.molimm.2012.01.006 · 3.00 Impact Factor
Show more