Type 2 diabetes mellitus in relation to global LINE-1 DNA methylation in peripheral blood: A cohort study

Martín‐Núñez, Gracia María; Rubio‐Martín, Elehazara; Cabrera-Mulero, Rebeca; Rojo-Martínez, Gemma; Olveira, Gabriel; Valdés, Sergio; Soriguer, Federico; Castaño, Luís; Morcillo, Sonsoles

doi:10.4161/15592294.2014.969617

Cited by 62 publications

(31 citation statements)

References 39 publications

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“…The CpG sites in a LINE‐1 promoter are normally heavily methylated to prevent retrotransposition . Recent studies have shown that methylation of the LINE‐1 elements is associated with an increased risk of worsening carbohydrate metabolism . It has been previously shown that overall DNA methylation of LINE‐1 elements could be considered as a risk factor for T2DM and its complications, independent of other established risk factors…”

Section: Why Epigenetics Is Important In Type 2 Diabetesmentioning

confidence: 99%

“…2 Recent studies have shown that methylation of the LINE-1 elements is associated with an increased risk of worsening carbohydrate metabolism. 3 It has been previously shown that overall DNA methylation of LINE-1 elements could be considered as a risk factor for T2DM and its complications, independent of other established risk factors. 4 Currently, it is not possible to predict accurately who will develop complications of T2DM.…”

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confidence: 99%

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Assessment of global long interspersed nucleotide element‐1 ( LINE ‐1) DNA methylation in a longitudinal cohort of type 2 diabetes mellitus (T2 DM ) individuals

Malipatil

Narayanan²,

Siddals

et al. 2018

Int J Clin Pract

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Introduction Recent studies have indicated that methylation of the LINE‐1 elements is associated with an increased risk of worsening carbohydrate metabolism. It has been shown that overall DNA methylation of LINE‐1 elements could be considered as a risk factor for T2DM and its complications, independent of other established risk factors. Methods A total of 794 T2DM individuals from Salford, UK were included in this study (60% men n = 470). All patients had clinical and metabolic variables measured in 2002 (baseline outcomes) and annually through to 2016. Global LINE‐1 DNA methylation was measured at four CpG sites. The QIAGEN PyroMark Q96 MD pyrosequencer was used to quantify methylation. Results The overall mean ± SD global LINE‐1 methylation was 75.81 ± 3.25%. Cross‐sectional linear regression analysis at baseline year 2002 showed that LINE‐1 methylation was a significant predictor of diastolic BP (adjusted beta coefficient β = −0.25), estimated glomerular filtration rate (eGFR) (β = −0.48) and cholesterol HDL ratio (β = −0.04). A 10% increase in LINE‐1 methylation was associated with a lower diastolic BP by 2.5 mm Hg, a lower eGFR by 4.8 ml/min/1.73 m2 and decreased cholesterol/HDL ratio by 0.4 mmol/L. Longitudinal analysis over the 14‐year‐follow‐up periods showed that global LINE‐1 methylation at baseline was associated with lower BMI in women [β = −0.25] and lower cholesterol: HDL ratio [β = −0.07]. A 10% increase in LINE‐1 methylation was associated with reduction in BMI by 2.5 kg/m2 in women and reduction in cholesterol:HDL ratio by 0.7 mmol/L. Conclusion In a 14‐year longitudinal cohort of T2DM individuals, relations between global LINE‐1 DNA methylation status and specific metabolic markers were seen. Also, a higher degree of DNA methylation was predictive of less weight gain over time in women.

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Section: Why Epigenetics Is Important In Type 2 Diabetesmentioning

confidence: 99%

mentioning

confidence: 99%

Assessment of global long interspersed nucleotide element‐1 ( LINE ‐1) DNA methylation in a longitudinal cohort of type 2 diabetes mellitus (T2 DM ) individuals

Malipatil

Narayanan²,

Siddals

et al. 2018

Int J Clin Pract

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“…Similarly, in-vitro studies in aortic endothelial cells from mice and in primary human endothelial cells prove that the activation of proinflammatory genes were continued for several days after the normalization of glucose concentration. 15 …”

Section: Metabolic Memory In Diabetesmentioning

confidence: 99%

Complications of diabetes: an unsolicited epigenetic memory

et al. 2015

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Diabetes is a multifactorial disease, characterized by hyperglycemia and insulin resistance. Diabetic microvascular end points such as retinopathy, cardiomyopathy and nephropathy; and macrovascular complications such as myocardial infarction and stroke are causing premature death in diabetic populations. Despite strong familial clustering is associated with diabetes, the essential role of epigenetic component in the development of diabetes and its complications is inevitable. Several clinical trials and experimental animal studies show the persistence of diabetic vascular complications even after the normalization of glucose in diabetic patients, indicating the role of epigenetic or metabolic memory. Although previous researches on diabetes implicated the role of reactive oxygen species in the pathogenesis and development of diabetic complications, lifestyle factors including diet and exercise and environmental factors are strongly associated in inducing epigenetic changes related to diabetic risk.

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“…Other epigenetic mechanisms have also been described in association with T2DM, such as reduced Long Interspersed Nucleotide Element 1 (LINE-1) DNA methylation [55]. DNA methylation measured in LINE-1 sequences has been considered a surrogate marker for global genome methylation.…”

Section: Introductionmentioning

confidence: 99%

“…Low methylation in LINE-1-repetitive elements has been associated with chromosomal instability as well as inflammatory process [56]. Notably, lower LINE-1 DNA methylation levels in peripheral blood cells were associated with a higher risk of T2DM, independently from other classic risk factors, highlighting the potential role for these epigenetic biomarkers as predictors of T2DM risk or other related metabolic disorders [55]. …”

Section: Introductionmentioning

confidence: 99%

Epigenetic mechanisms of endothelial dysfunction in type 2 diabetes

et al. 2015

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The development of type-2 diabetes mellitus (T2DM) and its complications is largely due to the complex interaction between genetic factors and environmental influences, mainly dietary habits and lifestyle, which can either accelerate or slow down disease progression. Recent findings suggest the potential involvement of epigenetic mechanisms as a crucial interface between the effects of genetic predisposition and environmental factors. The common denominator of environmental factors promoting T2DM development and progression is that they trigger an inflammatory response, promoting inflammation-mediated insulin resistance and endothelial dysfunction. Proinflammatory stimuli, including hyperglycemia, oxidative stress, and other inflammatory mediators, can affect epigenetic mechanisms, altering the expression of specific genes in target cells without changes in underlying DNA sequences. DNA methylation and post-translational histone modifications (PTHMs) are the most extensively investigated epigenetic mechanisms. Over the past few years, non-coding RNA, including microRNAs (miRNAs), have also emerged as key players in gene expression modulation. MiRNAs can be actively released or shed by cells in the bloodstream and taken up in active form by receiving cells, acting as efficient systemic communication tools. The miRNAs involved in modulation of inflammatory pathways (inflammamiRs), such as miR-146a, and those highly expressed in endothelial lineages and hematopoietic progenitor cells (angiomiRs), such as miR-126, are the most extensively studied circulating miRNAs in T2DM. However, data on circulating miRNA signatures associated with specific diabetic complications are still lacking. Since immune cells and endothelial cells are primarily involved in the vascular complications of T2DM, their relative contribution to circulating miRNA signatures needs to be elucidated. An integrated approach encompassing different epigenetic mechanisms would have the potential to provide new mechanistic insights into the genesis of diabetes and its severe vascular complications and identify a panel of epigenetic markers with diagnostic/prognostic and therapeutic relevance.

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Type 2 diabetes mellitus in relation to global LINE-1 DNA methylation in peripheral blood: A cohort study

Cited by 62 publications

References 39 publications

Assessment of global long interspersed nucleotide element‐1 ( LINE ‐1) DNA methylation in a longitudinal cohort of type 2 diabetes mellitus (T2 DM ) individuals

Assessment of global long interspersed nucleotide element‐1 ( LINE ‐1) DNA methylation in a longitudinal cohort of type 2 diabetes mellitus (T2 DM ) individuals

Complications of diabetes: an unsolicited epigenetic memory

Epigenetic mechanisms of endothelial dysfunction in type 2 diabetes

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