title: Differential Gene Expression in Diabetic Nephropathy in Individuals With Type 1 Diabetes.
abstract: BACKGROUND
  Diabetic nephropathy (DN) is the leading cause of end-stage renal disease (ESRD) in the United States.
  
  
  OBJECTIVE
  The aim of this study was to determine whether there were skin fibroblast gene expression differences between subjects with type 1 diabetes (T1D) with or without DN.
  
  
  METHODS
  This was a cross-sectional study conducted in the University of Minnesota.
  
  
  METHODS
  Study volunteers were 100 former participants of Genetics of Kidneys in Diabetes: 40 were diabetic nephropathy (DN) Controls, normoalbuminuric after ≥ 15 years of T1D; and 60 were DN Cases, 25 with proteinuria and 35 with ESRD.
  
  
  METHODS
  Skin fibroblasts were grown in high glucose (HG) for five passages (approximately 6 weeks).
  
  
  METHODS
  SF gene expression was assessed by transcriptome sequencing using the Illumina HiSeq 2000 platform. Pathway analyses tested directionally consistent group differences within the Kyoto Encyclopedia of Genes and Genomes pathways.
  
  
  RESULTS
  Eight pathways, all related to cell cycle and repair, were up-regulated in the DN Controls vs the DN Cases. These pathways markedly overlapped with the pathways up-regulated by HG in T1D monozygotic twins (MZT), but not in their non-T1D MZT. DN Cases showed statistical trends toward up-regulation of these pathways vs non-T1D MZT, but much less so than the DN Controls.
  
  
  CONCLUSIONS
  Together, these data suggest that SF from T1D patients undergo epigenetic modifications resulting in increased expression of genes in healing and repair pathways. These responses, much more robust in patients protected from DN, suggest that epigenetic factors are important in DN risk.
authors: Departments of Medicine and Pediatrics (M.L.C., M.M.), and Pediatrics and Laboratory Medicine and Pathology (Y.K.), University of Minnesota, Minneapolis, Minnesota 55455; Joslin Diabetes Center (A.B.G., A.S.K.), Harvard Medical School, Boston, Massachusetts 02115; Department of Genetics (J.H.M.), Institute for Biomedical Informatics, Department of Biostatistics and Epidemiology, Perelman School of Medicine, Dartmouth College, Hanover, New Hampshire 03755; Departments of Public Health Sciences (S.S.R.), and Bioinformatics and Genetics (J.C.M.), University of Virginia, Charlottesville, Virginia 22908; Department of Genetics (D.K.), Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota 55455; and JDRF (H.N.), New York, New York 10004.
authors: M Luiza
authors: ML
authors: Caramori
authors: Departments of Medicine and Pediatrics (M.L.C., M.M.), and Pediatrics and Laboratory Medicine and Pathology (Y.K.), University of Minnesota, Minneapolis, Minnesota 55455; Joslin Diabetes Center (A.B.G., A.S.K.), Harvard Medical School, Boston, Massachusetts 02115; Department of Genetics (J.H.M.), Institute for Biomedical Informatics, Department of Biostatistics and Epidemiology, Perelman School of Medicine, Dartmouth College, Hanover, New Hampshire 03755; Departments of Public Health Sciences (S.S.R.), and Bioinformatics and Genetics (J.C.M.), University of Virginia, Charlottesville, Virginia 22908; Department of Genetics (D.K.), Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota 55455; and JDRF (H.N.), New York, New York 10004.
authors: Youngki
authors: Y
authors: Kim
authors: Departments of Medicine and Pediatrics (M.L.C., M.M.), and Pediatrics and Laboratory Medicine and Pathology (Y.K.), University of Minnesota, Minneapolis, Minnesota 55455; Joslin Diabetes Center (A.B.G., A.S.K.), Harvard Medical School, Boston, Massachusetts 02115; Department of Genetics (J.H.M.), Institute for Biomedical Informatics, Department of Biostatistics and Epidemiology, Perelman School of Medicine, Dartmouth College, Hanover, New Hampshire 03755; Departments of Public Health Sciences (S.S.R.), and Bioinformatics and Genetics (J.C.M.), University of Virginia, Charlottesville, Virginia 22908; Department of Genetics (D.K.), Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota 55455; and JDRF (H.N.), New York, New York 10004.
authors: Allison B
authors: AB
authors: Goldfine
authors: Departments of Medicine and Pediatrics (M.L.C., M.M.), and Pediatrics and Laboratory Medicine and Pathology (Y.K.), University of Minnesota, Minneapolis, Minnesota 55455; Joslin Diabetes Center (A.B.G., A.S.K.), Harvard Medical School, Boston, Massachusetts 02115; Department of Genetics (J.H.M.), Institute for Biomedical Informatics, Department of Biostatistics and Epidemiology, Perelman School of Medicine, Dartmouth College, Hanover, New Hampshire 03755; Departments of Public Health Sciences (S.S.R.), and Bioinformatics and Genetics (J.C.M.), University of Virginia, Charlottesville, Virginia 22908; Department of Genetics (D.K.), Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota 55455; and JDRF (H.N.), New York, New York 10004.
authors: Jason H
authors: JH
authors: Moore
authors: Departments of Medicine and Pediatrics (M.L.C., M.M.), and Pediatrics and Laboratory Medicine and Pathology (Y.K.), University of Minnesota, Minneapolis, Minnesota 55455; Joslin Diabetes Center (A.B.G., A.S.K.), Harvard Medical School, Boston, Massachusetts 02115; Department of Genetics (J.H.M.), Institute for Biomedical Informatics, Department of Biostatistics and Epidemiology, Perelman School of Medicine, Dartmouth College, Hanover, New Hampshire 03755; Departments of Public Health Sciences (S.S.R.), and Bioinformatics and Genetics (J.C.M.), University of Virginia, Charlottesville, Virginia 22908; Department of Genetics (D.K.), Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota 55455; and JDRF (H.N.), New York, New York 10004.
authors: Stephen S
authors: SS
authors: Rich
authors: Departments of Medicine and Pediatrics (M.L.C., M.M.), and Pediatrics and Laboratory Medicine and Pathology (Y.K.), University of Minnesota, Minneapolis, Minnesota 55455; Joslin Diabetes Center (A.B.G., A.S.K.), Harvard Medical School, Boston, Massachusetts 02115; Department of Genetics (J.H.M.), Institute for Biomedical Informatics, Department of Biostatistics and Epidemiology, Perelman School of Medicine, Dartmouth College, Hanover, New Hampshire 03755; Departments of Public Health Sciences (S.S.R.), and Bioinformatics and Genetics (J.C.M.), University of Virginia, Charlottesville, Virginia 22908; Department of Genetics (D.K.), Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota 55455; and JDRF (H.N.), New York, New York 10004.
authors: Josyf C
authors: JC
authors: Mychaleckyj
authors: Departments of Medicine and Pediatrics (M.L.C., M.M.), and Pediatrics and Laboratory Medicine and Pathology (Y.K.), University of Minnesota, Minneapolis, Minnesota 55455; Joslin Diabetes Center (A.B.G., A.S.K.), Harvard Medical School, Boston, Massachusetts 02115; Department of Genetics (J.H.M.), Institute for Biomedical Informatics, Department of Biostatistics and Epidemiology, Perelman School of Medicine, Dartmouth College, Hanover, New Hampshire 03755; Departments of Public Health Sciences (S.S.R.), and Bioinformatics and Genetics (J.C.M.), University of Virginia, Charlottesville, Virginia 22908; Department of Genetics (D.K.), Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota 55455; and JDRF (H.N.), New York, New York 10004.
authors: David
authors: D
authors: Kirkpatrick
authors: Departments of Medicine and Pediatrics (M.L.C., M.M.), and Pediatrics and Laboratory Medicine and Pathology (Y.K.), University of Minnesota, Minneapolis, Minnesota 55455; Joslin Diabetes Center (A.B.G., A.S.K.), Harvard Medical School, Boston, Massachusetts 02115; Department of Genetics (J.H.M.), Institute for Biomedical Informatics, Department of Biostatistics and Epidemiology, Perelman School of Medicine, Dartmouth College, Hanover, New Hampshire 03755; Departments of Public Health Sciences (S.S.R.), and Bioinformatics and Genetics (J.C.M.), University of Virginia, Charlottesville, Virginia 22908; Department of Genetics (D.K.), Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota 55455; and JDRF (H.N.), New York, New York 10004.
authors: Helen
authors: H
authors: Nickerson
authors: Departments of Medicine and Pediatrics (M.L.C., M.M.), and Pediatrics and Laboratory Medicine and Pathology (Y.K.), University of Minnesota, Minneapolis, Minnesota 55455; Joslin Diabetes Center (A.B.G., A.S.K.), Harvard Medical School, Boston, Massachusetts 02115; Department of Genetics (J.H.M.), Institute for Biomedical Informatics, Department of Biostatistics and Epidemiology, Perelman School of Medicine, Dartmouth College, Hanover, New Hampshire 03755; Departments of Public Health Sciences (S.S.R.), and Bioinformatics and Genetics (J.C.M.), University of Virginia, Charlottesville, Virginia 22908; Department of Genetics (D.K.), Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota 55455; and JDRF (H.N.), New York, New York 10004.
authors: Andrzej S
authors: AS
authors: Krolewski
authors: Departments of Medicine and Pediatrics (M.L.C., M.M.), and Pediatrics and Laboratory Medicine and Pathology (Y.K.), University of Minnesota, Minneapolis, Minnesota 55455; Joslin Diabetes Center (A.B.G., A.S.K.), Harvard Medical School, Boston, Massachusetts 02115; Department of Genetics (J.H.M.), Institute for Biomedical Informatics, Department of Biostatistics and Epidemiology, Perelman School of Medicine, Dartmouth College, Hanover, New Hampshire 03755; Departments of Public Health Sciences (S.S.R.), and Bioinformatics and Genetics (J.C.M.), University of Virginia, Charlottesville, Virginia 22908; Department of Genetics (D.K.), Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota 55455; and JDRF (H.N.), New York, New York 10004.
authors: Michael
authors: M
authors: Mauer
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002478:Cells, Cultured; D003430:Cross-Sectional Studies; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000235:genetics* / Q000473:pathology; D003928:Diabetic Nephropathies / Q000235:genetics* / Q000473:pathology; D005260:Female; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D061251:Primary Cell Culture; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D014430:Twins, Monozygotic