18 January 2010
ByAppeared in BioNews 541
A new study by scientists at the University of Cambridge, UK, has indicated that people in the later stages of heart disease carry specific changes in three key genes. However, these alterations to the genes are not permanent mutations, rather, they consist of a reversible change that may be influenced by the environment and diet, and may be responsible for integrating lifestyle and dietary signals to later heart failure.
The investigation, lead by Dr Roger Foo at the university's Division of Cardiovascular Medicine, compared the DNA from healthy hearts with DNA from patients undergoing cardiac transplant for end-stage heart failure. The scientists were looking specifically for a pattern on the DNA known as methylation. Methylation - where a chemical group (called a methyl group) attaches itself to a gene - is one of the ways in which genes are controlled in the body. Varying how much methylation there is can mean that a gene in otherwise good working order may stop functioning, or become over-active - both of which can be harmful depending on the circumstances.
Dr Foo and colleagues identified three genes important in heart function that showed different patterns of methylation in heathly compared to diseased hearts. Two of these, the AMOTL2 and PECAM1 genes, functioned less efficiently in diseased hearts; while the ARHGAP24 gene was found to be overactive.
Evidence indicates that while person to person variation in methylation patterns is partly inherited, it may change throughout life as well. For example, identical twin studies show that although twins are born with identical genes and indistinguishable DNA methylation patterns, as they age, they exhibit remarkable differences in the way their genes are methylated, which in turn influenced how their otherwise identical genes actually functioned and their susceptibility to disease. Because methylation of DNA is something that can be altered by the environment and diet, differential DNA methylation may be responsible for integrating genes and environment - nature and nurture - in the progression of heart disease. There is already evidence to suggest that methylated genes could be implicated in other complex diseases like as schizophrenia, diabetes and inflammatory bowel disease. The effect of variable methylation may also answer a question that has previously been difficult to shed light on - how can the same diseases vary from person to person in symptoms, progression and risk of fatality?
Because the reseachers studied DNA from already diseased hearts, they next aim to determine whether the DNA methylation changes that they identified could be an actual cause of, rather than a late side-effect in the progression of heart failure. They hope that unravelling such additional complex layers in the way genes are controlled will improve patient options for therapy and disease management.