Epigenetic Modifications Linked to T2D, the Heritability Gap, and Potential Therapeutic Targets

Szabo, Monica Iudita Maria; Máté, Beáta; Csép, Katalin; Benedek, Theodora

doi:10.1007/s10528-018-9863-8

Cited by 11 publications

(9 citation statements)

References 140 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…There is a need to develop biomarkers to detect early steps in the pathophysiologic progression of T2D, as well as to elucidate underlying mechanisms of the disease [24]. Genetics, epigenetics, as well as non-genetic factors (diet, lifestyle) are involved in the pathogenesis of dysglycaemia and T2D [25].…”

Section: Discussionmentioning

confidence: 99%

Insulin Sensitivity Is Associated with Lipoprotein Lipase (LPL) and Catenin Delta 2 (CTNND2) DNA Methylation in Peripheral White Blood Cells in Non-Diabetic Young Women

Arpón

Santos

Milagro

et al. 2019

IJMS

View full text Add to dashboard Cite

Hyperglycaemia and type 2 diabetes (T2D) are associated with impaired insulin secretion and/or insulin action. Since few studies have addressed the relation between DNA methylation patterns with elaborated surrogates of insulin secretion/sensitivity based on the intravenous glucose tolerance test (IVGTT), the aim of this study was to evaluate the association between DNA methylation and an insulin sensitivity index based on IVGTT (calculated insulin sensitivity index (CSi)) in peripheral white blood cells from 57 non-diabetic female volunteers. The CSi and acute insulin response (AIR) indexes, as well as the disposition index (DI = CSi × AIR), were estimated from abbreviated IVGTT in 49 apparently healthy Chilean women. Methylation levels were assessed using the Illumina Infinium Human Methylation 450k BeadChip. After a statistical probe filtering, the two top CpGs whose methylation was associated with CSi were cg04615668 and cg07263235, located in the catenin delta 2 (CTNND2) and lipoprotein lipase (LPL) genes, respectively. Both CpGs conjointly predicted insulin sensitivity status with an area under the curve of 0.90. Additionally, cg04615668 correlated with homeostasis model assessment insulin-sensitivity (HOMA-S) and AIR, whereas cg07263235 was associated with plasma creatinine and DI. These results add further insights into the epigenetic regulation of insulin sensitivity and associated complications, pointing the CTNND2 and LPL genes as potential underlying epigenetic biomarkers for future risk of insulin-related diseases.

show abstract

Section: Discussionmentioning

confidence: 99%

Insulin Sensitivity Is Associated with Lipoprotein Lipase (LPL) and Catenin Delta 2 (CTNND2) DNA Methylation in Peripheral White Blood Cells in Non-Diabetic Young Women

Arpón

Santos

Milagro

et al. 2019

IJMS

View full text Add to dashboard Cite

show abstract

“…Post-translational changes in histone proteins can alter the chromatin conformation and gene regulation, contributing thus to the metabolic disease phenotype. Their influence on the development of obesity and T2D has been well-described elsewhere [6], and will not be covered in the present review, which is specifically focused on DNA methylation.…”

Section: Introductionmentioning

confidence: 99%

Nutritional Factors, DNA Methylation, and Risk of Type 2 Diabetes and Obesity: Perspectives and Challenges

Parrillo

Spinelli

Nicolò

et al. 2019

IJMS

View full text Add to dashboard Cite

A healthy diet improves life expectancy and helps to prevent common chronic diseases such as type 2 diabetes (T2D) and obesity. The mechanisms driving these effects are not fully understood, but are likely to involve epigenetics. Epigenetic mechanisms control gene expression, maintaining the DNA sequence, and therefore the full genomic information inherited from our parents, unchanged. An interesting feature of epigenetic changes lies in their dynamic nature and reversibility. Accordingly, they are susceptible to correction through targeted interventions. Here we will review the evidence supporting a role for nutritional factors in mediating metabolic disease risk through DNA methylation changes. Special emphasis will be placed on the potential of using DNA methylation traits as biomarkers to predict risk of obesity and T2D as well as on their response to dietary and pharmacological (epi-drug) interventions.

show abstract

“…Previously, the identification of diabetes-linked genes was the product of quantitative trait mapping (QTL), obtained through the cross of genetically engineered mice ( 132 – 134 ). Over the past decade as the cost and availability of sequencing technology has improved, GWAS have identified more than 60 loci for T1D ( 135 ) and more than 240 associated with T2D ( 136 ), with the hereditability of each now explaining approximately 15% ( 137 ) and 25-80% ( 138 ) of the disease-risk for each subtype, respectively.…”

Section: The Role Of Candidate Gene and Gwas Approaches In The Study Of Diabetesmentioning

confidence: 99%

Genome Editing Human Pluripotent Stem Cells to Model β-Cell Disease and Unmask Novel Genetic Modifiers

2021

View full text Add to dashboard Cite

A mechanistic understanding of the genetic basis of complex diseases such as diabetes mellitus remain elusive due in large part to the activity of genetic disease modifiers that impact the penetrance and/or presentation of disease phenotypes. In the face of such complexity, rare forms of diabetes that result from single-gene mutations (monogenic diabetes) can be used to model the contribution of individual genetic factors to pancreatic β-cell dysfunction and the breakdown of glucose homeostasis. Here we review the contribution of protein coding and non-protein coding genetic disease modifiers to the pathogenesis of diabetes subtypes, as well as how recent technological advances in the generation, differentiation, and genome editing of human pluripotent stem cells (hPSC) enable the development of cell-based disease models. Finally, we describe a disease modifier discovery platform that utilizes these technologies to identify novel genetic modifiers using induced pluripotent stem cells (iPSC) derived from patients with monogenic diabetes caused by heterozygous mutations.

show abstract

Epigenetic Modifications Linked to T2D, the Heritability Gap, and Potential Therapeutic Targets

Cited by 11 publications

References 140 publications

Insulin Sensitivity Is Associated with Lipoprotein Lipase (LPL) and Catenin Delta 2 (CTNND2) DNA Methylation in Peripheral White Blood Cells in Non-Diabetic Young Women

Insulin Sensitivity Is Associated with Lipoprotein Lipase (LPL) and Catenin Delta 2 (CTNND2) DNA Methylation in Peripheral White Blood Cells in Non-Diabetic Young Women

Nutritional Factors, DNA Methylation, and Risk of Type 2 Diabetes and Obesity: Perspectives and Challenges

Genome Editing Human Pluripotent Stem Cells to Model β-Cell Disease and Unmask Novel Genetic Modifiers

Contact Info

Product

Resources

About