DNA methylation predicts diabetes risk
Sofia Dolotovskaya, N+1
An international research team has shown that obesity causes epigenetic changes in a variety of sites throughout the genome, including genes associated with lipid and lipoprotein metabolism and inflammation. By the nature of these changes, as it turned out, it is possible to predict the risk of developing type 2 diabetes – and with more confidence than by such traditional markers as the type of obesity or blood glucose. Article by Wahl et al. Epigenome-wide association study of body mass index, and the adverse outcomes of adiposity is published in the journal Nature.
About 1.5 billion people are overweight or obese and have an increased risk of developing type 2 diabetes, cardiovascular diseases and metabolic disorders. Previous studies have shown that obesity causes epigenetic changes (namely, changes in the status of DNA methylation) in some loci: for example, in adipose tissue and skeletal muscles.
The authors of the new article conducted a genome-wide association study to find out how body mass index is associated with DNA methylation. The analysis included 5,387 people of European and Indian origin. In total, methylation at 187 genetic loci was associated with the body mass index. For these loci, the authors compared the levels of DNA methylation in different tissues: blood, adipose tissue, liver, pancreas, spleen and muscles. Although, in general, the level of methylation in the blood and liver well reflected the level of methylation in other tissues, in some cases the effect was specific to the type of tissue. For example, for 91 loci, the association of methylation with body mass index was the strongest in adipose tissue.
The analysis of associations showed that the detected changes in DNA methylation are mainly a consequence, not a cause of obesity. The authors identified 38 genes whose expression depends on the detected epigenetic changes. The effect of methylation was observed for the expression of these genes in blood, adipose tissue and liver. Among these genes were genes involved in lipid and lipoprotein metabolism, amino acid transport, and inflammatory signaling pathways.
It also turned out that changes in methylation can predict the risk of developing type 2 diabetes. At the same time, the association of diabetes risk with methylation turned out to be stronger for many loci and independent of associations of the risk of developing the disease with traditional markers, such as type of obesity, fasting blood glucose or elevated blood insulin levels. In other words, the predictive power of epigenetic markers turned out to be higher than the predictive power of traditional markers of the risk of developing type 2 diabetes – and, importantly, independent of them.
As the authors conclude, these results may in the future allow the use of DNA methylation as a marker for identifying people with "metabolically unfavorable" types of obesity who have an increased risk of developing type 2 diabetes.
Previously, scientists have shown that obesity causes epigenetic changes in men's sperm, which can be transmitted to their children and increase their likelihood of developing obesity. Recently, this epigenetic inheritance of the tendency to obesity has also been confirmed in experiments on mice.
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22.12.2016