Our genes play a huge role in everything about us, and it's thought that they don't change much over time. But many changes can happen to DNA throughout a lifetime, which leave marks on the genome. Epigenetic tags can involve chemical groups or structural alterations in the genome, for example, and they can have a significant impact on gene expression without changing the sequence of DNA. Now scientists have learned more about how epigenetic changes are involved in the development of type 2 diabetes, and whether those changes can lead to the disorder, or only occur after the metabolic disorder has arisen. The study, which was reported in Nature Communications, provides support for the idea that epigenetic changes can cause type 2 diabetes.
This "extensive" work has confirmed previous, smaller studies. The research also identified novel genes that are related to type 2 diabetes, noted study leader Charlotte Ling, professor of diabetes and epigenetics at Lund University's Diabetes Center (LUDC). "Our hope is that with the help of these results, we can develop methods that can be used to prevent type 2 diabetes."
In this work, the investigators assessed the epigenetic features of cells that generate insulin, the beta cells of the pancreas, from 25 type 2 diabetes patients and 75 unaffected individuals. They focused on 5,584 sites in the genome, and found that people with abnormally high levels of blood sugar have similar epigenetic signatures as people with type 2 diabetes; high blood sugar is a known risk factor for the metabolic disorder.
"Those of us who study epigenetics have long tried to understand whether epigenetic changes cause type 2 diabetes or if the changes occur after the disease has already developed. Because we saw the same epigenetic changes in people with type 2 diabetes and individuals at risk for the disease, we conclude that these changes may contribute to the development of type 2 diabetes," said first study author Tina Rönn, a researcher at LUDC.
The work suggested that in type 2 diabetics, there are about 200 genes in which expression changes compared to unaffected people. The RHOT1 gene in particular carried epigenetic changes in type 2 diabetics and has a crucial role in the release of insulin from pancreatic beta cells.
The researchers found that RHOT1 expression was absent in beta cells in a rat model of diabetes, noted Rönn.
The scientists are interested in identifying a biomarker that will show who is at risk for developing type 2 diabetes. They determined from samples of a group of 540 people that epigenetic changes can show who will develop type 2 diabetes.
"If we succeed in developing an epigenetic biomarker, we can identify individuals with epigenetic changes before they become ill. These individuals can, for example, receive personalized lifestyle advice that can reduce their risk of disease, or we can develop methods that aim to correct the activity of certain genes using epigenetic editing," added Ling.
Sources: Lund University, Nature Communications