The potential use of DNA methylation biomarkers to identify risk and progression of type 2 diabetes

Frontiers in Endocrinology

Volumn 6, Issue MAR, 2015, Pages

  Gillberg, Linn ^a,b   Ling, Charlotte ^c  

^a Rigshospitalet   (Denmark)

^b UNIVERSITY OF COPENHAGEN   (Denmark)

^c LUND UNIVERSITY DIABETES CENTRE   (Sweden)

Author keywords

Biomarkers; DNA methylation; Epigenetics; Prediction; Prevention; Type 2 diabetes

Indexed keywords

CYTOSINE; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; KRUPPEL LIKE FACTOR; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA COACTIVATOR 1ALPHA; SEPTIN; SMALL UNTRANSLATED RNA;

AGE; BODY MASS; DISEASE COURSE; DNA METHYLATION; EPIGENETICS; GENE EXPRESSION; GENETIC PREDISPOSITION; GENETIC VARIABILITY; GLUCOSE TOLERANCE; HUMAN; IMPAIRED GLUCOSE TOLERANCE; INSULIN RESISTANCE; LIFESTYLE MODIFICATION; NON INSULIN DEPENDENT DIABETES MELLITUS; OBESITY; PHYSICAL ACTIVITY; REVIEW; RISK;

EID: 84926625108     PISSN: None     EISSN: 16642392     Source Type: Journal    
DOI: 10.3389/fendo.2015.00043     Document Type: Review

References (85)

1. Abdul-Ghani MA, Tripathy D, DeFronzo RA. Contributions of beta-cell dysfunction and insulin resistance to the pathogenesis of impaired glucose tolerance and impaired fasting glucose. Diabetes Care (2006) 29(5):1130-9. doi:10.2337/dc05-2179
2. Perseghin G, Ghosh S, Gerow K, Shulman GI. Metabolic defects in lean nondiabetic offspring of NIDDM parents: a cross-sectional study. Diabetes (1997) 46(6):1001-9. doi:10.2337/diab.46.6.1001
3. Hu FB, Manson JE, Stampfer MJ, Colditz G, Liu S, Solomon CG, et al. Diet, lifestyle, and the risk of type 2 diabetes mellitus in women. N Engl J Med (2001) 345(11):790-7. doi:10.1056/NEJMoa010492
4. Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med (2002) 346(6):393-403. doi:10.1056/NEJMoa012512
5. Tuomilehto J, Lindstrom J, Eriksson JG, Valle TT, Hamalainen H, Ilanne-Parikka P, et al. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med (2001) 344(18):1343-50. doi:10.1056/NEJM200105033441801
6. Al-Mahdawi S, Virmouni SA, Pook MA. The emerging role of 5-hydroxymethylcytosine in neurodegenerative diseases. Front Neurosci (2014) 8:397. doi:10.3389/fnins.2014.00397
7. Barres R, Zierath JR. DNA methylation in metabolic disorders. Am J Clin Nutr (2011) 93(4):897S-900S. doi:10.3945/ajcn.110.001933
8. Dimopoulos K, Gimsing P, Gronbaek K. The role of epigenetics in the biology of multiple myeloma. Blood Cancer J (2014) 4:e207. doi:10.1038/bcj.2014.29
9. Gautrey HE, van Otterdijk SD, Cordell HJ, Mathers JC, Strathdee G. DNA methylation abnormalities at gene promoters are extensive and variable in the elderly and phenocopy cancer cells. FASEB J (2014) 28(7):3261-72. doi:10.1096/fj.13-246173
10. Ling C, Groop L. Epigenetics: a molecular link between environmental factors and type 2 diabetes. Diabetes (2009) 58(12):2718-25. doi:10.2337/db09-1003
11. Dayeh T, Volkov P, Salo S, Hall E, Nilsson E, Olsson AH, et al. Genome-wide DNA methylation analysis of human pancreatic islets from type 2 diabetic and non-diabetic donors identifies candidate genes that influence insulin secretion. PLoS Genet (2014) 10(3):e1004160. doi:10.1371/journal.pgen.1004160
12. Ling C, Del GS, Lupi R, Ronn T, Granhall C, Luthman H, et al. Epigenetic regulation of PPARGC1A in human type 2 diabetic islets and effect on insulin secretion. Diabetologia (2008) 51(4):615-22. doi:10.1007/s00125-007-0916-5
13. Nilsson E, Jansson PA, Perfilyev A, Volkov P, Pedersen M, Svensson MK, et al. Altered DNA methylation and differential expression of genes influencing metabolism and inflammation in adipose tissue from subjects with type 2 diabetes. Diabetes (2014) 63(9):2962-76. doi:10.2337/db13-1459
14. Nitert MD, Dayeh T, Volkov P, Elgzyri T, Hall E, Nilsson E, et al. Impact of an exercise intervention on DNA methylation in skeletal muscle from first-degree relatives of patients with type 2 diabetes. Diabetes (2012) 61(12):3322-32. doi:10.2337/db11-1653
15. Yang BT, Dayeh TA, Kirkpatrick CL, Taneera J, Kumar R, Groop L, et al. Insulin promoter DNA methylation correlates negatively with insulin gene expression and positively with HbA(1c) levels in human pancreatic islets. Diabetologia (2011) 54(2):360-7. doi:10.1007/s00125-010-1967-6
16. Dick KJ, Nelson CP, Tsaprouni L, Sandling JK, Aissi D, Wahl S, et al. DNA methylation and body-mass index: a genome-wide analysis. Lancet (2014) 383(9933):1990-8. doi:10.1016/S0140-6736(13)62674-4
17. Franks PW, Ling C. Epigenetics and obesity: the devil is in the details. BMC Med (2010) 8:88. doi:10.1186/1741-7015-8-88
18. Ling C, Poulsen P, Simonsson S, Ronn T, Holmkvist J, Almgren P, et al. Genetic and epigenetic factors are associated with expression of respiratory chain component NDUFB6 in human skeletal muscle. J Clin Invest (2007) 117(11):3427-35. doi:10.1172/JCI30938
19. Ronn T, Poulsen P, Hansson O, Holmkvist J, Almgren P, Nilsson P, et al. Age influences DNA methylation and gene expression of COX7A1 in human skeletal muscle. Diabetologia (2008) 51(7):1159-68. doi:10.1007/s00125-008-1018-8
20. Ronn T, Volkov P, Davegardh C, Dayeh T, Hall E, Olsson AH, et al. A six months exercise intervention influences the genome-wide DNA methylation pattern in human adipose tissue. PLoS Genet (2013) 9(6):e1003572. doi:10.1371/journal.pgen.1003572
21. Hales CN, Barker DJ. Type 2 (non-insulin-dependent) diabetes mellitus: the thrifty phenotype hypothesis. Diabetologia (1992) 35(7):595-601. doi:10.1007/BF00400248
22. The International Diabetes Federation (IDF). IDF Diabetes Atlas. 6th ed. (2014). Available from: http://www.diabetesatlas.org/
23. Vaag A, Brons C, Gillberg L, Hansen NS, Hjort L, Arora GP, et al. Genetic, nongenetic and epigenetic risk determinants in developmental programming of type 2 diabetes. Acta Obstet Gynecol Scand (2014) 93(11):1099-108. doi:10.1111/aogs.12494
24. Laaksonen MA, Knekt P, Rissanen H, Harkanen T, Virtala E, Marniemi J, et al. The relative importance of modifiable potential risk factors of type 2 diabetes: a meta-analysis of two cohorts. Eur J Epidemiol (2010) 25(2):115-24. doi:10.1007/s10654-009-9405-0
25. DeFronzo RA. Pathogenesis of type 2 (non-insulin dependent) diabetes mellitus: a balanced overview. Diabetologia (1992) 35(4):389-97. doi:10.1007/BF00401208
26. Eriksson J, Franssila-Kallunki A, Ekstrand A, Saloranta C, Widen E, Schalin C, et al. Early metabolic defects in persons at increased risk for non-insulin-dependent diabetes mellitus. N Engl J Med (1989) 321(6):337-43. doi:10.1056/NEJM198908103210601
27. Dimas AS, Lagou V, Barker A, Knowles JW, Magi R, Hivert MF, et al. Impact of type 2 diabetes susceptibility variants on quantitative glycemic traits reveals mechanistic heterogeneity. Diabetes (2014) 63(6):2158-71. doi:10.2337/db13-0949
28. Fraga MF, Ballestar E, Paz MF, Ropero S, Setien F, Ballestar ML, et al. Epigenetic differences arise during the lifetime of monozygotic twins. Proc Natl Acad Sci U S A (2005) 102(30):10604-9. doi:10.1073/pnas.0500398102
29. Bell JT, Tsai PC, Yang TP, Pidsley R, Nisbet J, Glass D, et al. Epigenome-wide scans identify differentially methylated regions for age and age-related phenotypes in a healthy ageing population. PLoS Genet (2012) 8(4):e1002629. doi:10.1371/journal.pgen.1002629
30. Christensen BC, Houseman EA, Marsit CJ, Zheng S, Wrensch MR, Wiemels JL, et al. Aging and environmental exposures alter tissue-specific DNA methylation dependent upon CpG island context. PLoS Genet (2009) 5(8):e1000602. doi:10.1371/journal.pgen.1000602
31. Garagnani P, Bacalini MG, Pirazzini C, Gori D, Giuliani C, Mari D, et al. Methylation of ELOVL2 gene as a new epigenetic marker of age. Aging Cell (2012) 11(6):1132-4. doi:10.1111/acel.12005
32. Heyn H, Li N, Ferreira HJ, Moran S, Pisano DG, Gomez A, et al. Distinct DNA methylomes of newborns and centenarians. Proc Natl Acad Sci U S A (2012) 109(26):10522-7. doi:10.1073/pnas.1120658109
33. Horvath S, Zhang Y, Langfelder P, Kahn RS, Boks MP, van EK, et al. Aging effects on DNA methylation modules in human brain and blood tissue. Genome Biol (2012) 13(10):R97. doi:10.1186/gb-2012-13-10-r97
34. Horvath S. DNA methylation age of human tissues and cell types. Genome Biol (2013) 14(10):R115. doi:10.1186/gb-2013-14-10-r115
35. Johansson A, Enroth S, Gyllensten U. Continuous aging of the human DNA methylome throughout the human lifespan. PLoS One (2013) 8(6):e67378. doi:10.1371/journal.pone.0067378
36. Steegenga WT, Boekschoten MV, Lute C, Hooiveld GJ, de Groot PJ, Morris TJ, et al. Genome-wide age-related changes in DNA methylation and gene expression in human PBMCs. Age (Dordr) (2014) 36(3):9648. doi:10.1007/s11357-014-9648-x
37. Teschendorff AE, Menon U, Gentry-Maharaj A, Ramus SJ, Weisenberger DJ, Shen H, et al. Age-dependent DNA methylation of genes that are suppressed in stem cells is a hallmark of cancer. Genome Res (2010) 20(4):440-6. doi:10.1101/gr.103606.109
38. Levine ME. Modeling the rate of senescence: can estimated biological age predict mortality more accurately than chronological age? J Gerontol A Biol Sci Med Sci (2013) 68(6):667-74. doi:10.1093/gerona/gls233
39. Hannum G, Guinney J, Zhao L, Zhang L, Hughes G, Sadda S, et al. Genome-wide methylation profiles reveal quantitative views of human aging rates. Mol Cell (2013) 49(2):359-67. doi:10.1016/j.molcel.2012.10.016
40. Marioni RE, Shah S, McRae AF, Chen BH, Colicino E, Harris SE, et al. DNA methylation age of blood predicts all-cause mortality in later life. Genome Biol (2015) 16(1):25. doi:10.1186/s13059-015-0584-6
41. Leonard AE, Kelder B, Bobik EG, Chuang LT, Lewis CJ, Kopchick JJ, et al. Identification and expression of mammalian long-chain PUFA elongation enzymes. Lipids (2002) 37(8):733-40. doi:10.1007/s11745-002-0955-6
42. Small KS, Hedman AK, Grundberg E, Nica AC, Thorleifsson G, Kong A, et al. Identification of an imprinted master trans regulator at the KLF14 locus related to multiple metabolic phenotypes. Nat Genet (2011) 43(6):561-4. doi:10.1038/ng.833
43. Voight BF, Scott LJ, Steinthorsdottir V, Morris AP, Dina C, Welch RP, et al. Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis. Nat Genet (2010) 42(7):579-89. doi:10.1038/ng.609
44. Teslovich TM, Musunuru K, Smith AV, Edmondson AC, Stylianou IM, Koseki M, et al. Biological, clinical and population relevance of 95 loci for blood lipids. Nature (2010) 466(7307):707-13. doi:10.1038/nature09270
45. Day K, Waite LL, Thalacker-Mercer A, West A, Bamman MM, Brooks JD, et al. Differential DNA methylation with age displays both common and dynamic features across human tissues that are influenced by CpG landscape. Genome Biol (2013) 14(9):R102. doi:10.1186/gb-2013-14-9-r102
46. Zykovich A, Hubbard A, Flynn JM, Tarnopolsky M, Fraga MF, Kerksick C, et al. Genome-wide DNA methylation changes with age in disease-free human skeletal muscle. Aging Cell (2014) 13(2):360-6. doi:10.1111/acel.12180
47. Wang X, Zhu H, Snieder H, Su S, Munn D, Harshfield G, et al. Obesity related methylation changes in DNA of peripheral blood leukocytes. BMC Med (2010) 8:87. doi:10.1186/1741-7015-8-87
48. Na YK, Hong HS, Lee DH, Lee WK, Kim DS. Effect of body mass index on global DNA methylation in healthy Korean women. Mol Cells (2014) 37(6):467-72. doi:10.14348/molcells.2014.0073
49. Keller M, Kralisch S, Rohde K, Schleinitz D, Dietrich A, Schon MR, et al. Global DNA methylation levels in human adipose tissue are related to fat distribution and glucose homeostasis. Diabetologia (2014) 57(11):2374-83. doi:10.1007/s00125-014-3356-z
50. Agha G, Houseman EA, Kelsey KT, Eaton CB, Buka SL, Loucks EB. Adiposity is associated with DNA methylation profile in adipose tissue. Int J Epidemiol (2014). doi:10.1093/ije/dyu236
51. Ling C, Poulsen P, Carlsson E, Ridderstrale M, Almgren P, Wojtaszewski J, et al. Multiple environmental and genetic factors influence skeletal muscle PGC-1alpha and PGC-1beta gene expression in twins. J Clin Invest (2004) 114(10):1518-26. doi:10.1172/JCI21889
52. Ribel-Madsen R, Fraga MF, Jacobsen S, Bork-Jensen J, Lara E, Calvanese V, et al. Genome-wide analysis of DNA methylation differences in muscle and fat from monozygotic twins discordant for type 2 diabetes. PLoS One (2012) 7(12):e51302. doi:10.1371/journal.pone.0051302
53. Barres R, Osler ME, Yan J, Rune A, Fritz T, Caidahl K, et al. Non-CpG methylation of the PGC-1alpha promoter through DNMT3B controls mitochondrial density. Cell Metab (2009) 10(3):189-98. doi:10.1016/j.cmet.2009.07.011
54. Brons C, Jacobsen S, Nilsson E, Ronn T, Jensen CB, Storgaard H, et al. Deoxyribonucleic acid methylation and gene expression of PPARGC1A in human muscle is influenced by high-fat overfeeding in a birth-weight-dependent manner. J Clin Endocrinol Metab (2010) 95(6):3048-56. doi:10.1210/jc.2009-2413
55. Gillberg L, Jacobsen SC, Ronn T, Brons C, Vaag A. PPARGC1A DNA methylation in subcutaneous adipose tissue in low birth weight subjects-impact of 5days of high-fat overfeeding. Metabolism (2014) 63(2):263-71. doi:10.1016/j.metabol.2013.10.003
56. Jorgensen SW, Brons C, Bluck L, Hjort L, Faerch K, Thankamony A, et al. Metabolic response to 36 hours of fasting in young men born small vs appropriate for gestational age. Diabetologia (2015) 58(1):178-87. doi:10.1007/s00125-014-3406-6
57. Gillberg L, Jacobsen S, Ribel-Madsen R, Gjesing AP, Boesgaard TW, Ling C, et al. Does DNA methylation of PPARGC1A influence insulin action in first degree relatives of patients with type 2 diabetes? PLoS One (2013) 8(3):e58384. doi:10.1371/journal.pone.0058384
58. Sookoian S, Rosselli MS, Gemma C, Burgueno AL, Fernandez GT, Castano GO, et al. Epigenetic regulation of insulin resistance in nonalcoholic fatty liver disease: impact of liver methylation of the peroxisome proliferator-activated receptor gamma coactivator 1alpha promoter. Hepatology (2010) 52(6):1992-2000. doi:10.1002/hep.23927
59. Clarke-Harris R, Wilkin TJ, Hosking J, Pinkney J, Jeffery AN, Metcalf BS, et al. PGC1alpha promoter methylation in blood at 5-7 years predicts adiposity from 9 to 14 years (earlybird 50). Diabetes (2014) 63(7):2528-37. doi:10.2337/db13-0671
60. Hidalgo B, Irvin MR, Sha J, Zhi D, Aslibekyan S, Absher D, et al. Epigenome-wide association study of fasting measures of glucose, insulin, and HOMA-IR in the genetics of lipid lowering drugs and diet network study. Diabetes (2014) 63(2):801-7. doi:10.2337/db13-1100
61. Yuan W, Xia Y, Bell CG, Yet I, Ferreira T, Ward KJ, et al. An integrated epigenomic analysis for type 2 diabetes susceptibility loci in monozygotic twins. Nat Commun (2014) 5:5719. doi:10.1038/ncomms6719
62. Toperoff G, Aran D, Kark JD, Rosenberg M, Dubnikov T, Nissan B, et al. Genome-wide survey reveals predisposing diabetes type 2-related DNA methylation variations in human peripheral blood. Hum Mol Genet (2012) 21(2):371-83. doi:10.1093/hmg/ddr472
63. Esguerra JL, Mollet IG, Salunkhe VA, Wendt A, Eliasson L. Regulation of pancreatic beta cell stimulus-secretion coupling by microRNAs. Genes (Basel) (2014) 5(4):1018-31. doi:10.3390/genes5041018
64. Esguerra JL, Eliasson L. Functional implications of long non-coding RNAs in the pancreatic islets of Langerhans. Front Genet (2014) 5:209. doi:10.3389/fgene.2014.00209
65. Guay C, Regazzi R. Circulating microRNAs as novel biomarkers for diabetes mellitus. Nat Rev Endocrinol (2013) 9(9):513-21. doi:10.1038/nrendo.2013.86
66. Bell CG, Teschendorff AE, Rakyan VK, Maxwell AP, Beck S, Savage DA. Genome-wide DNA methylation analysis for diabetic nephropathy in type 1 diabetes mellitus. BMC Med Genomics (2010) 3:33. doi:10.1186/1755-8794-3-33
67. Andersen GS, Thybo T, Cederberg H, Oresic M, Esteller M, Zorzano A, et al. The DEXLIFE study methods: identifying novel candidate biomarkers that predict progression to type 2 diabetes in high risk individuals. Diabetes Res Clin Pract (2014) 106(2):383-9. doi:10.1016/j.diabres.2014.07.025
68. Brunetti A, Chiefari E, Foti D. Recent advances in the molecular genetics of type 2 diabetes mellitus. World J Diabetes (2014) 5(2):128-40. doi:10.4239/wjd.v5.i2.128
69. Lyssenko V, Jorgensen T, Gerwien RW, Hansen T, Rowe MW, McKenna MP, et al. Validation of a multi-marker model for the prediction of incident type 2 diabetes mellitus: combined results of the Inter99 and Botnia studies. Diab Vasc Dis Res (2012) 9(1):59-67. doi:10.1177/1479164111424762
70. Paneni F, Costantino S, Cosentino F. Molecular mechanisms of vascular dysfunction and cardiovascular biomarkers in type 2 diabetes. Cardiovasc Diagn Ther (2014) 4(4):324-32. doi:10.3978/j.issn.2223-3652.2014.08.02
71. Epigenomics AG. Epigenomics-Finding Cancer Early. (2011). Available from: www.epigenomics.com
72. deVos T, Tetzner R, Model F, Weiss G, Schuster M, Distler J, et al. Circulating methylated SEPT9 DNA in plasma is a biomarker for colorectal cancer. Clin Chem (2009) 55(7):1337-46. doi:10.1373/clinchem.2008.115808
73. Model F, Osborn N, Ahlquist D, Gruetzmann R, Molnar B, Sipos F, et al. Identification and validation of colorectal neoplasia-specific methylation markers for accurate classification of disease. Mol Cancer Res (2007) 5(2):153-63. doi:10.1158/1541-7786.MCR-06-0034
74. Ravelli AC, van der Meulen JH, Michels RP, Osmond C, Barker DJ, Hales CN, et al. Glucose tolerance in adults after prenatal exposure to famine. Lancet (1998) 351(9097):173-7. doi:10.1016/S0140-6736(05)79096-6
75. Vaag AA, Grunnet LG, Arora GP, Brons C. The thrifty phenotype hypothesis revisited. Diabetologia (2012) 55(8):2085-8. doi:10.1007/s00125-012-2589-y
76. Mikeska T, Craig JM. DNA methylation biomarkers: cancer and beyond. Genes (Basel) (2014) 5(3):821-64. doi:10.3390/genes5030821
77. Ficz G. New insights into mechanisms that regulate DNA methylation patterning. J Exp Biol (2015) 218(Pt 1):14-20. doi:10.1242/jeb.107961
78. Dayeh TA, Olsson AH, Volkov P, Almgren P, Ronn T, Ling C. Identification of CpG-SNPs associated with type 2 diabetes and differential DNA methylation in human pancreatic islets. Diabetologia (2013) 56(5):1036-46. doi:10.1007/s00125-012-2815-7
79. Olsson AH, Volkov P, Bacos K, Dayeh T, Hall E, Nilsson EA, et al. Genome-wide associations between genetic and epigenetic variation influence mRNA expression and insulin secretion in human pancreatic islets. PLoS Genet (2014) 10(11):e1004735. doi:10.1371/journal.pgen.1004735
80. Jacobsen SC, Brons C, Bork-Jensen J, Ribel-Madsen R, Yang B, Lara E, et al. Effects of short-term high-fat overfeeding on genome-wide DNA methylation in the skeletal muscle of healthy young men. Diabetologia (2012) 55(12):3341-9. doi:10.1007/s00125-012-2717-8
81. Kundaje A, Meuleman W, Ernst J, Bilenky M, Yen A, Heravi-Moussavi A, et al. Integrative analysis of 111 reference human epigenomes. Nature (2015) 518(7539):317-30. doi:10.1038/nature14248
82. Heijmans BT, Tobi EW, Stein AD, Putter H, Blauw GJ, Susser ES, et al. Persistent epigenetic differences associated with prenatal exposure to famine in humans. Proc Natl Acad Sci U S A (2008) 105(44):17046-9. doi:10.1073/pnas.0806560105
83. Jacobsen SC, Gillberg L, Bork-Jensen J, Ribel-Madsen R, Lara E, Calvanese V, et al. Young men with low birthweight exhibit decreased plasticity of genome-wide muscle DNA methylation by high-fat overfeeding. Diabetologia (2014) 57(6):1154-8. doi:10.1007/s00125-014-3198-8
84. Ozanne SE, Constancia M. Mechanisms of disease: the developmental origins of disease and the role of the epigenotype. Nat Clin Pract Endocrinol Metab (2007) 3(7):539-46. doi:10.1038/ncpendmet0531
85. Schultz NS, Broholm C, Gillberg L, Mortensen B, Jorgensen SW, Schultz HS, et al. Impaired leptin gene expression and release in cultured preadipocytes isolated from individuals born with low birth weight. Diabetes (2014) 63(1):111-21. doi:10.2337/db13-0621