​Epigenetic Changes and Disease – What Is the Connection?

Previous research has shown that there is a connection between epigenetic changes and some of our common illnesses. But what does this connection mean? A new study shows that external factors, such as lifestyle aspects, often affect both the epigenetic pattern and cause the disease. The results have been published in PLOS Genetics.

sperm, brain tumours, Common drugs, diabetes, chronic wounds, magnetism, intestinal tumours, molecular scissors, disease, genetic, immune cells, drug development, Diabetes, Antibiotic, hydrogen generation, chronic obstructive pulmonary disease, malaria, photosynthesis, kidney failure, Brain tumours, mental health, blood cancer, cancer, dementia, cancer treatment, antibiotic resistance, blood vessel leakage, quantum simulations, atrial fibrillation, batteries, goiter treatment, terahertz radiation, organic materials , Guild of European Research Intensive Universities, gene copies, social anxiety, blue light screens, ‘Our hope is that these findings will make it possible to discover a way to selectively inhibit the TGF-beta signals that stimulate tumour development without knocking out the signals that inhibit tumour development, and that this can eventually be used in the fight against cancer,’ says Eleftheria Vasilaki, postdoctoral researcher at Ludwig Institute for Cancer Research at Uppsala University and lead author of the study. TGF-beta regulates cell growth and specialisation, in particular during foetal development. In the context of tumour development, TGF-beta has a complicated role. Initially, it inhibits tumour formation because it inhibits cell division and stimulates cell death. At a late stage of tumour development, however, TGF-beta stimulates proliferation and metastasis of tumour cells and thereby accelerates tumour formation. TGF-beta’s signalling mechanisms and role in tumour development have been studied at the Ludwig Institute for Cancer Research at Uppsala University for the past 30 years. Recent discoveries at the Institute, now published in the current study in Science Signaling, explain part of the mechanism by which TGF-beta switches from suppressing to enhancing tumour development. Uppsala researchers, in collaboration with a Japanese research team, discovered that TGF-beta along with the oncoprotein Ras, which is often activated in tumours, affects members of the p53 family. The p53 protein plays a key role in regulating tumour development and is often altered – mutated – in tumours. TGF-beta and Ras suppress the effect of mutated p53, thereby enhancing the effect of another member of the p53 family, namely delta-Np63, which in turn stimulates tumour development and metastasis.

The risk of developing our most common diseases depends on inheritance, lifestyle and environment. In recent years, epigenetic changes have also been assumed to increase the risk of various diseases. Epigenetic changes are chemical modifications of the DNA that turn genes on or off. In the current study from Uppsala University, researchers show that epigenetic changes mainly occur in response to a disease, rather than being an underlying causal risk factor.

Today, we know that the environment we live in and our lifestyle can lead to epigenetic changes as well as to increased risk for various diseases. Earlier studies have shown that there is a strong link between epigenetic changes and the risk of various diseases such as myocardial infarction, asthma, rheumatism and schizophrenia. However, it has not been known whether such epigenetic changes are the cause of the diseases or if they arise due to the disease, or whether both epigenetic changes and the development of a disease are due to external factors, such as a person’s lifestyle.

In the current study, the researchers investigated the relationship between genetic variation, epigenetic changes, and lifestyle factors in relation to biological markers for cardiovascular diseases, so called biomarkers.

“The results show that the link between epigenetic changes and disease status is largely due to external factors, such as the lifestyle, or due to the genetic variation we inherit from our parents,” says Åsa Johansson, researcher at the Department of Immunology, Genetics and Pathology, who led the study.

For example, the researchers showed that smoking affects both the epigenetic pattern and the presence of different disease biomarkers.

“Such cases can easily be interpreted as the epigenetic changes causing the disease, when it’s actually smoking that is the causal factor,” says Åsa Johansson.

Similarly, the researchers could see that genetic variation also affected the epigenetic pattern and many disease biomarkers. However, they found no evidence that epigenetic changes could affect the disease risk. The researchers hope that the study should contribute to a better understanding of what role epigenetic changes play in disease pathogenesis, where epigenetic changes should be recognised as markers of different exposures rather than something causing disease.

Source : Uppsala University