Gene Expression Differences in Skin Fibroblasts in Identical Twins Discordant for Type 1 Diabetes
- M. Luiza Caramori1⇓,
- Youngki Kim2,
- Jason H. Moore3,
- Stephen S. Rich4,
- Josyf C. Mychaleckyj4,
- Nobuaki Kikyo5 and
- Michael Mauer1
- 1Departments of Medicine and Pediatrics, University of Minnesota, Minneapolis, Minnesota
- 2Departments of Pediatrics and Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota
- 3Department of Genetics, Dartmouth College, Lebanon, New Hampshire
- 4Department of Public Health Sciences, University of Virginia, Charlottesville, Virginia
- 5Department of Medicine and Stem Cell Institute, University of Minnesota, Minneapolis, Minnesota
- Corresponding author: M. Luiza Caramori, .
Clinical studies suggest metabolic memory to hyperglycemia. We tested whether diabetes leads to persistent systematic in vitro gene expression alterations in patients with type 1 diabetes (T1D) compared with their monozygotic, nondiabetic twins. Microarray gene expression was determined in skin fibroblasts (SFs) of five twin pairs cultured in high glucose (HG) for ∼6 weeks. The Exploratory Visual Analysis System tested group differences in gene expression levels within KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways. An overabundance of differentially expressed genes was found in eight pathways: arachidonic acid metabolism (P = 0.003849), transforming growth factor-β signaling (P = 0.009167), glutathione metabolism (P = 0.01281), glycosylphosphatidylinositol anchor (P = 0.01949), adherens junction (P = 0.03134), dorsal-ventral axis formation (P = 0.03695), proteasome (P = 0.04327), and complement and coagulation cascade (P = 0.04666). Several genes involved in epigenetic mechanisms were also differentially expressed. All differentially expressed pathways and all the epigenetically relevant differentially expressed genes have previously been related to HG in vitro or to diabetes and its complications in animal and human studies. However, this is the first in vitro study demonstrating diabetes-relevant gene expression differences between T1D-discordant identical twins. These SF gene expression differences, persistent despite the HG in vitro conditions, likely reflect “metabolic memory”, and discordant identical twins thus represent an excellent model for studying diabetic epigenetic processes in humans.
- Received May 9, 2011.
- Accepted December 15, 2011.
- © 2012 by the American Diabetes Association.
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