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Differential Methylation of TCF7L2 Promoter in Peripheral Blood DNA in Newly Diagnosed, Drug-Naïve Patients with Type 2 Diabetes

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 patt...

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Autores principales: Canivell, Silvia, Ruano, Elena G., Sisó-Almirall, Antoni, Kostov, Belchin, González-de Paz, Luis, Fernandez-Rebollo, Eduardo, Hanzu, Felicia A., Párrizas, Marcelina, Novials, Anna, Gomis, Ramon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4051650/
https://www.ncbi.nlm.nih.gov/pubmed/24914535
http://dx.doi.org/10.1371/journal.pone.0099310
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author Canivell, Silvia
Ruano, Elena G.
Sisó-Almirall, Antoni
Kostov, Belchin
González-de Paz, Luis
Fernandez-Rebollo, Eduardo
Hanzu, Felicia A.
Párrizas, Marcelina
Novials, Anna
Gomis, Ramon
author_facet Canivell, Silvia
Ruano, Elena G.
Sisó-Almirall, Antoni
Kostov, Belchin
González-de Paz, Luis
Fernandez-Rebollo, Eduardo
Hanzu, Felicia A.
Párrizas, Marcelina
Novials, Anna
Gomis, Ramon
author_sort Canivell, Silvia
collection PubMed
description 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.
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spelling pubmed-40516502014-06-18 Differential Methylation of TCF7L2 Promoter in Peripheral Blood DNA in Newly Diagnosed, Drug-Naïve Patients with Type 2 Diabetes Canivell, Silvia Ruano, Elena G. Sisó-Almirall, Antoni Kostov, Belchin González-de Paz, Luis Fernandez-Rebollo, Eduardo Hanzu, Felicia A. Párrizas, Marcelina Novials, Anna Gomis, Ramon PLoS One Research Article 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. Public Library of Science 2014-06-10 /pmc/articles/PMC4051650/ /pubmed/24914535 http://dx.doi.org/10.1371/journal.pone.0099310 Text en © 2014 Canivell et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Canivell, Silvia
Ruano, Elena G.
Sisó-Almirall, Antoni
Kostov, Belchin
González-de Paz, Luis
Fernandez-Rebollo, Eduardo
Hanzu, Felicia A.
Párrizas, Marcelina
Novials, Anna
Gomis, Ramon
Differential Methylation of TCF7L2 Promoter in Peripheral Blood DNA in Newly Diagnosed, Drug-Naïve Patients with Type 2 Diabetes
title Differential Methylation of TCF7L2 Promoter in Peripheral Blood DNA in Newly Diagnosed, Drug-Naïve Patients with Type 2 Diabetes
title_full Differential Methylation of TCF7L2 Promoter in Peripheral Blood DNA in Newly Diagnosed, Drug-Naïve Patients with Type 2 Diabetes
title_fullStr Differential Methylation of TCF7L2 Promoter in Peripheral Blood DNA in Newly Diagnosed, Drug-Naïve Patients with Type 2 Diabetes
title_full_unstemmed Differential Methylation of TCF7L2 Promoter in Peripheral Blood DNA in Newly Diagnosed, Drug-Naïve Patients with Type 2 Diabetes
title_short Differential Methylation of TCF7L2 Promoter in Peripheral Blood DNA in Newly Diagnosed, Drug-Naïve Patients with Type 2 Diabetes
title_sort differential methylation of tcf7l2 promoter in peripheral blood dna in newly diagnosed, drug-naïve patients with type 2 diabetes
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4051650/
https://www.ncbi.nlm.nih.gov/pubmed/24914535
http://dx.doi.org/10.1371/journal.pone.0099310
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