Altered intragenic DNA methylation of HOOK2 gene in adipose tissue from individuals with obesity and type 2 diabetes

Failure in glucose response to insulin is a common pathology associated with obesity. In this study, we analyzed the genome wide DNA methylation profile of visceral adipose tissue (VAT) samples in a population of individuals with obesity and assessed whether differential methylation profiles are ass...

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Published in:PloS one 2017-12, Vol.12 (12), p.e0189153-e0189153
Main Authors: Rodríguez-Rodero, Sandra, Menéndez-Torre, Edelmiro, Fernández-Bayón, Gustavo, Morales-Sánchez, Paula, Sanz, Lourdes, Turienzo, Estrella, González, Juan José, Martinez-Faedo, Ceferino, Suarez-Gutiérrez, Lorena, Ares, Jessica, Díaz-Naya, Lucia, Martin-Nieto, Alicia, Fernández-Morera, Juan L, Fraga, Mario F, Delgado-Álvarez, Elías
Format: Article
Language:English
Subjects:
Adipose tissue
Analysis
Biology and life sciences
Body fat
Cancer
Care and treatment
CpG islands
Cyclin-dependent kinases
Deoxyribonucleic acid
Diabetes
Diabetes mellitus
DNA
DNA methylation
Endocrinology
Epigenetics
Females
Gastric bypass
Gender aspects
Gender differences
Gene expression
Genomes
Health aspects
Insulin
Insulin resistance
Internet
Kinases
Laboratories
Males
Medicine and Health Sciences
Metabolism
Methylation
Nutrition
Obesity
Oncology
Physical Sciences
Proteins
Sex differences
Signal transduction
Surgery
Transcription factors
Type 2 diabetes
Weight control
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Summary:Failure in glucose response to insulin is a common pathology associated with obesity. In this study, we analyzed the genome wide DNA methylation profile of visceral adipose tissue (VAT) samples in a population of individuals with obesity and assessed whether differential methylation profiles are associated with the presence of type 2 diabetes (T2D). More than 485,000 CpG genome sites from VAT samples from women with obesity undergoing gastric bypass (n = 18), and classified as suffering from type 2 diabetes (T2D) or not (no type 2 diabetes, NT2D), were analyzed using DNA methylation arrays. We found significant differential methylation between T2D and NT2D samples in 24 CpGs that map with sixteen genes, one of which, HOOK2, demonstrated a significant correlation between differentially hypermethylated regions on the gene body and the presence of type 2 diabetes. This was validated by pyrosequencing in a population of 91 samples from both males and females with obesity. Furthermore, when these results were analyzed by gender, female T2D samples were found hypermethylated at the cg04657146-region and the cg 11738485-region of HOOK2 gene, whilst, interestingly, male samples were found hypomethylated in this latter region. The differential methylation profile of the HOOK2 gene in individuals with T2D and obesity might be related to the attendant T2D, but further studies are required to identify the potential role of HOOK2 gene in T2D disease. The finding of gender differences in T2D methylation of HOOK2 also warrants further investigation.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0189153