title: Differential methylation of TCF7L2 promoter in peripheral blood DNA in newly diagnosed, drug-naïve patients with type 2 diabetes.
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.
authors.affiliation: Department of Endocrinology and Nutrition, Hospital Clinic, Barcelona, Spain; Les Corts Primary Health Care Centre, PHC Research Group, IDIBAPS, Barcelona, Spain; Diabetes and Obesity Laboratory, IDIBAPS, Barcelona, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: Canivell
authors.affiliation: Diabetes and Obesity Laboratory, IDIBAPS, Barcelona, Spain; CIBERDEM, Barcelona, Spain.
authors.forename: Elena G
authors.initials: EG
authors.lastname: Ruano
authors.affiliation: Les Corts Primary Health Care Centre, PHC Research Group, IDIBAPS, Barcelona, Spain; University of Barcelona, Barcelona, Spain.
authors.forename: Antoni
authors.initials: A
authors.lastname: Sisó-Almirall
authors.affiliation: Les Corts Primary Health Care Centre, PHC Research Group, IDIBAPS, Barcelona, Spain.
authors.forename: Belchin
authors.initials: B
authors.lastname: Kostov
authors.affiliation: Les Corts Primary Health Care Centre, PHC Research Group, IDIBAPS, Barcelona, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: González-de Paz
authors.affiliation: Diabetes and Obesity Laboratory, IDIBAPS, Barcelona, Spain; CIBERDEM, Barcelona, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Fernandez-Rebollo
authors.affiliation: Department of Endocrinology and Nutrition, Hospital Clinic, Barcelona, Spain; Diabetes and Obesity Laboratory, IDIBAPS, Barcelona, Spain.
authors.forename: Felicia A
authors.initials: FA
authors.lastname: Hanzu
authors.affiliation: Diabetes and Obesity Laboratory, IDIBAPS, Barcelona, Spain.
authors.forename: Marcelina
authors.initials: M
authors.lastname: Párrizas
authors.affiliation: Department of Endocrinology and Nutrition, Hospital Clinic, Barcelona, Spain; Diabetes and Obesity Laboratory, IDIBAPS, Barcelona, Spain; CIBERDEM, Barcelona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Novials
authors.affiliation: Department of Endocrinology and Nutrition, Hospital Clinic, Barcelona, Spain; Diabetes and Obesity Laboratory, IDIBAPS, Barcelona, Spain; CIBERDEM, Barcelona, Spain; University of Barcelona, Barcelona, Spain.
authors.forename: Ramon
authors.initials: R
authors.lastname: Gomis
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D018899:CpG Islands / Q000235:genetics; D004247:DNA / Q000097:blood*; D019175:DNA Methylation / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D055432:Metabolomics; D011401:Promoter Regions, Genetic; D058118:Transcription Factor 7-Like 2 Protein / Q000235:genetics*
chemical_list: C544894:TCF7L2 protein, human; D058118:Transcription Factor 7-Like 2 Protein; D004247:DNA