INTRODUCTION: Type 2 Diabetes (T2D) is a common chronic disease with substantial disease burden and economic impact. Lifestyle changes can significantly alter the course of the disease, if detected at an early stage. DNA methylation signature may serve as a biomarker for early detection of increased T2D risk. DESIGN: DNA methylation profiling was performed using the Illumina Infinium Human Methylation 450K Bead chip array in 24 normoglycemic Old Order Amish (OOA) individuals who later developed Impaired Fasting Glucose (IFG) (cases), and 24 OOA individuals who remained normoglycemic after an average follow up of 10 years (controls). Cases and controls were matched on age, sex, BMI, baseline fasting glucose, and glucose level after 2 h from 75 g Oral Glucose Tolerance Test (OGTT). RESULTS: Association analysis found no significant difference in either global methylation or individual probe methylation between cases and controls, however, the top 34 suggestive significant sites were located in genes with interesting biological links to T2D and glycemic traits. These genes include BTC that plays a role in pancreatic cell proliferation and insulin secretion, ITGA1 a known bone mineral density gene that was recently found to be associated also with T2D and glycemic traits, and may explain the link between T2D and BMD, and RPTOR and TSC2 both of which are part of insulin signaling pathway. CONCLUSIONS: These results may shed light on the initiation and development of hyperglycemia and T2D and help to identify high risk individuals for early intervention; however, further studies are required for validation.
INTRODUCTION: Type 2 Diabetes (T2D) is a common chronic disease with substantial disease burden and economic impact. Lifestyle changes can significantly alter the course of the disease, if detected at an early stage. DNA methylation signature may serve as a biomarker for early detection of increased T2D risk. DESIGN: DNA methylation profiling was performed using the Illumina Infinium Human Methylation 450K Bead chip array in 24 normoglycemic Old Order Amish (OOA) individuals who later developed Impaired Fasting Glucose (IFG) (cases), and 24 OOA individuals who remained normoglycemic after an average follow up of 10 years (controls). Cases and controls were matched on age, sex, BMI, baseline fasting glucose, and glucose level after 2 h from 75 g Oral Glucose Tolerance Test (OGTT). RESULTS: Association analysis found no significant difference in either global methylation or individual probe methylation between cases and controls, however, the top 34 suggestive significant sites were located in genes with interesting biological links to T2D and glycemic traits. These genes include BTC that plays a role in pancreatic cell proliferation and insulin secretion, ITGA1 a known bone mineral density gene that was recently found to be associated also with T2D and glycemic traits, and may explain the link between T2D and BMD, and RPTOR and TSC2 both of which are part of insulin signaling pathway. CONCLUSIONS: These results may shed light on the initiation and development of hyperglycemia and T2D and help to identify high risk individuals for early intervention; however, further studies are required for validation.
Entities:
Keywords:
DNA methylation; Impaired Fasting Glucose (IFG); Old Order Amish (OOA)
Authors: Alan R Shuldiner; Jeffrey R O'Connell; Kevin P Bliden; Amish Gandhi; Kathleen Ryan; Richard B Horenstein; Coleen M Damcott; Ruth Pakyz; Udaya S Tantry; Quince Gibson; Toni I Pollin; Wendy Post; Afshin Parsa; Braxton D Mitchell; Nauder Faraday; William Herzog; Paul A Gurbel Journal: JAMA Date: 2009-08-26 Impact factor: 56.272
Authors: Liana K Billings; Yi-Hsiang Hsu; Rachel J Ackerman; Josée Dupuis; Benjamin F Voight; Laura J Rasmussen-Torvik; Serge Hercberg; Mark Lathrop; Daniel Barnes; Claudia Langenberg; Jennie Hui; Mao Fu; Nabila Bouatia-Naji; Cecile Lecoeur; Ping An; Patrik K Magnusson; Ida Surakka; Samuli Ripatti; Lene Christiansen; Christine Dalgård; Lasse Folkersen; Elin Grundberg; Per Eriksson; Jaakko Kaprio; Kirsten Ohm Kyvik; Nancy L Pedersen; Ingrid B Borecki; Michael A Province; Beverley Balkau; Philippe Froguel; Alan R Shuldiner; Lyle J Palmer; Nick Wareham; Pierre Meneton; Toby Johnson; James S Pankow; David Karasik; James B Meigs; Douglas P Kiel; Jose C Florez Journal: Diabetes Date: 2012-06-14 Impact factor: 9.337
Authors: Bertha Hidalgo; M Ryan Irvin; Jin Sha; Degui Zhi; Stella Aslibekyan; Devin Absher; Hemant K Tiwari; Edmond K Kabagambe; Jose M Ordovas; Donna K Arnett Journal: Diabetes Date: 2013-10-29 Impact factor: 9.461
Authors: Tasnim Dayeh; Petr Volkov; Sofia Salö; Elin Hall; Emma Nilsson; Anders H Olsson; Clare L Kirkpatrick; Claes B Wollheim; Lena Eliasson; Tina Rönn; Karl Bacos; Charlotte Ling Journal: PLoS Genet Date: 2014-03-06 Impact factor: 5.917
Authors: T Muka; J Nano; T Voortman; K V E Braun; S Ligthart; S Stranges; W M Bramer; J Troup; R Chowdhury; A Dehghan; O H Franco Journal: Nutr Metab Cardiovasc Dis Date: 2016-04-14 Impact factor: 4.222
Authors: Wei Yuan; Yudong Xia; Christopher G Bell; Idil Yet; Teresa Ferreira; Kirsten J Ward; Fei Gao; A Katrina Loomis; Craig L Hyde; Honglong Wu; Hanlin Lu; Yuan Liu; Kerrin S Small; Ana Viñuela; Andrew P Morris; María Berdasco; Manel Esteller; M Julia Brosnan; Panos Deloukas; Mark I McCarthy; Sally L John; Jordana T Bell; Jun Wang; Tim D Spector Journal: Nat Commun Date: 2014-12-12 Impact factor: 14.919