Heart disease linked to epigenetics

We’ve known for some time that if you abuse your body (smoke too much, drink too much, become obese, don’t sleep enough, stress-out a lot, don’t exercise), you’re more likely to develop heart disease. It’s also been known that heart disease has genetic effects, or that certain genes are involved with heart disease. A new study at Cambridge University (England) has found the link between the environmental factors and the genetic effects. The name of the link is DNA methylation, which unfortunately is neither well known by people in general nor easy to explain. Yet it is one of the most fundamental processes in cell biology.

One of the most important things that living cells must do is reproduce – make copies of themselves so the organism can grow or maintain itself. Equally important, each cell must reproduce without losing its inherent characteristics. A heart cell, when it splits in two during mitosis, must produce two identical heart cells. The questions are: How does a cell become a heart cell (differentiate)? And how does that differentiation transfer when the cells duplicate? The answer is (at least in part): Through DNA methylation.

Our DNA is composed of two nucleotide strands in the familiar double helix, and forming genes through sequences of four bases: adenine, thymine, cytosine, and guanine (abbreviated A, T, C, and G). The genes are the master code of the cell (and the body), but they do not act alone. The genes lay down the plans for making every part of a cell, but the cell needs to interact with the environment (other cells, body signals like hormones, etc.) to help select which genes to use. This is where DNA methylation comes in. It’s a chemical process (grossly simplified) whereby proteins that interact with the environment attach to parts of certain genes a ‘mark’ or ‘marker’ that indicates the gene is not to be used (the word in genetic biology is ‘expressed’). This marker is a molecule of methyl (CH3), which is attached to certain cytosine-guanine (CG) base pairs.

This methyl marker is so important to cell biology that some scientists think of it as the ‘fifth base.’ It is also key to the primary mechanism of epigenetics, where characteristics of a cell that are changed by the environment are continued as cells reproduce by mitosis. (This is not to be confused with genetic inheritance, which occurs when cells reproduce by meiosis – the old egg and sperm routine.) One of the things DNA methylation does is help cells differentiate. As an organism develops, cells take on different roles – they differentiate – into heart cells, for example. When this happens, certain genes are disabled by methylation. They are marked to not be expressed. Thereafter, when the cell splits to reproduce, the methyl markers are also copied, and they help determine that two heart cells (and no other) are created.

Much the same thing apparently happens with other characteristics that are ‘marked’ on the genes in response to environmental influence – including characteristics associated with heart disease. This is where the Cambridge study begins. The research is based on studies of samples taken from two groups: Men with heart disease that died after heart transplants, and people with healthy hearts that died in traffic accidents. After examining and then comparing the genome from each group, they found ‘markers’ from DNA methylation at significant heart related gene locations only in the tissue from diseased hearts.

According to the study’s first author, Dr Mehregan Movassagh of the University of Cambridge: “DNA methylation is a mechanism by which the environment and diet alters the expression of certain human genes, and has been the explanation for why, for instance, identical twins may have differing features and differ in their susceptibility to disease, despite having an identical set of genes.”

It is also a very widespread process, occurring in plants and insects as well as vertebrates. In honey bees, for example, it is the reduction in DNA methylation that occurs as a result of feeding royal jelly which causes genetically identical larvae to develop into a queen, rather than a worker.

Epigenetic factors, such as DNA methylation, are currently the focus of much medical research because they offer further insight into disease than simply looking at our genes.

“We already know that several genes play an important role in heart failure. Researchers have looked at mutations in these genes and sometimes don’t see any, so it could be methylation, not mutation, which is responsible for the altered expression that leads to disease. This opens a new window on the link between genome and disease,” Movassagh says.

[Source: EurekAlert]

The results of the Cambridge research establish for the first time a link, for example, between abuse of our body and its epigenetic expression in heart disease. At this point, the understanding of the link is crude. Lots more work is necessary to identify specific genes and their CG patterns (which are methylated and which not) in relation to heart disease. Even more work is needed to explore the pathways by which environmental pressures (say, obesity) come to affect proteins that methylate DNA. However, this relatively obvious study opens the door to some very important future work in molecular biology – one of those doors that will someday lead to various treatments of heart disease.

Research Spectrum

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