Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/61783
Title: Differential methylation of TCF7L2 promoter in peripheral blood DNA in newly diagnosed, drug-naïve patients with type 2 diabetes
Author: Canivell, S.
Ruano, Elena G.
Sisó Almirall, Antoni
Kostov, B.
González de Paz, L.
Fernández-Rebollo, E.
Hanzu, Felicia A.
Párrizas, Marcelina
Novials, Anna
Gomis, Ramon, 1946-
Keywords: Diabetis
Epidemiologia genètica
Metilació
ADN
Marcadors genètics
Diabetes
Genetic epidemiology
Methylation
DNA
Genetic markers
Issue Date: 10-Jun-2014
Publisher: Public Library of Science (PLoS)
Abstract: TCF7L2 is the susceptibility gene for Type 2 diabetes (T2D) with the largest effect on disease risk that has been discovered to date. However, the mechanisms by which TCF7L2 contributes to the disease remain largely elusive. In addition, epigenetic mechanisms, such as changes in DNA methylation patterns, might have a role in the pathophysiology of T2D. This study aimed to investigate the differences in terms of DNA methylation profile of TCF7L2 promoter gene between type 2 diabetic patients and age- and Body Mass Index (BMI)- matched controls. We included 93 type 2 diabetic patients that were recently diagnosed for T2D and exclusively on diet (without any pharmacological treatment). DNA was extracted from whole blood and DNA methylation was assessed using the Sequenom EpiTYPER system. Type 2 diabetic patients were more insulin resistant than their matched controls (mean HOMA IR 2.6 vs 1.8 in controls, P<0.001) and had a poorer beta-cell function (mean HOMA B 75.7 vs. 113.6 in controls, P<0.001). Results showed that 59% of the CpGs analyzed in TCF7L2 promoter had significant differences between type 2 diabetic patients and matched controls. In addition, fasting glucose, HOMA-B, HOMA-IR, total cholesterol and LDL-cholesterol correlated with methylation in specific CpG sites of TCF7L2 promoter. After adjustment by age, BMI, gender, physical inactivity, waist circumference, smoking status and diabetes status uniquely fasting glucose, total cholesterol and LDL-cholesterol remained significant. Taken together, newly diagnosed, drug-naïve type 2 diabetic patients display specific epigenetic changes at the TCF7L2 promoter as compared to age- and BMI-matched controls. Methylation in TCF7L2 promoter is further correlated with fasting glucose in peripheral blood DNA, which sheds new light on the role of epigenetic regulation of TCF7L2 in T2D.
Note: Reproducció del document publicat a: http://dx.doi.org/10.1371/journal.pone.0099310
It is part of: PLoS One, 2014, vol. 9, num. 6, p. e99310
Related resource: http://dx.doi.org/10.1371/journal.pone.0099310
URI: http://hdl.handle.net/2445/61783
ISSN: 1932-6203
Appears in Collections:Articles publicats en revistes (Medicina)

Files in This Item:
File Description SizeFormat 
643563.pdf205.55 kBAdobe PDFView/Open


This item is licensed under a Creative Commons License Creative Commons