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. 2014 Oct;9(10):1322-8.
doi: 10.4161/15592294.2014.969617.

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

Gracia María Martín-Núñez  1 , Elehazara Rubio-Martín, Rebeca Cabrera-Mulero, Gemma Rojo-Martínez, Gabriel Olveira, Sergio Valdés, Federico Soriguer, Luis Castaño, Sonsoles Morcillo
Affiliations

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

Gracia María Martín-Núñez et al. Epigenetics. 2014 Oct.

Abstract

In the last years, epigenetic processes have emerged as a promising area of complex diseases research. DNA methylation measured in Long Interspersed Nucleotide Element 1 (LINE-1) sequences has been considered a surrogate marker for global genome methylation. New findings have suggested the potential involvement of epigenetic mechanisms in Type 2 diabetes (T2DM) as a crucial interface between the effects of genetic predisposition and environmental influences. Our study evaluated whether global DNA methylation predicted increased risk from T2DM or other carbohydrate metabolism disorders in a cohort study. We used a prospective cohort intervention study and a control group. We collected phenotypic, anthropometric, biochemical, and nutritional information from all subjects. Global LINE-1 DNA methylation was quantified by pyrosequencing technology. Subjects that did not improve their carbohydrate metabolism status showed lower levels of global LINE-1 DNA methylation (63.9 ± 1.7 vs. 64.7 ± 2.4) and they practiced less intense physical activity (5.8% vs. 21.5%). Logistic regression analyses showed a significant association between LINE-1 DNA methylation and metabolic status after adjustment for sex, age, BMI, and physical activity. Our study showed that lower LINE-1 DNA methylation levels were associated with a higher risk metabolic status worsening, independent of other classic risk factors. This finding highlights the potential role for epigenetic biomarkers as predictors of T2DM risk or other related metabolic disorders.

Keywords: BMI, body mass index.; CVD, cardiovascular diseases; DNA methylation; IFG, impaired fasting glucose; IGT, impaired glucose tolerance; LINE-1; LINE-1, Long Interspersed Nucleotide Element 1; T2DM, Type 2 diabetes mellitus; cohort study; diabetes; peripheral blood cell.

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Figures

Figure 1.
Figure 1.
ROC curve for the different risk prediction models.
See this image and copyright information in PMC

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