15 January 2010
The new study published in PLoS ONE has linked epigenetic changes with cardiomyopathy, a form of heart disease characterised by weakening of the heart or a change in muscle structure that diminishes the ability of the heart to function effectively. There are three main forms of cardiomyopathy – dilated, where the heart becomes enlarged and weakened; hypertrophic, where the heart muscle becomes thickened, forcing the heart to work harder to pump blood out of the heart; and restrictive, where the heart muscle becomes stiff and hence unable to properly fill with blood (for more information, see The Cardiomyopathy Association).
Differences in DNA methylation are currently understood to be involved in the control of gene expression, which may in turn contribute to complex disease susceptibility or progression. Strong links have already been found between differential methylation and cancer, and there are efforts underway to examine the link with other complex diseases such as schizophrenia, diabetes and inflammatory bowel disease.
Researchers in Cambridge have found differences in DNA methylation in hearts from a small number of people with end-stage cardiomyopathy who were undergoing heart transplantation and the healthy hearts of age-matched victims of road traffic accidents [Movassagh M et al. (2010) PLoS ONE 5(1): e8564, doi:10.1371/journal.pone.0008564].The differential methylation correlated with differences in gene expression patterns between the heart failure and control groups.
They conclude that differential DNA methylation, along with other epigenetic mechanisms, may influence the development of heart failure in response to environmental factors, including dietary influences, effectively representing a ‘missing link’ between genetic and environmental causes of heart failure. The researchers also comment that, although certain genes are known to play an important role in heart failure, sometimes mutations are not found in those genes and thus it may be methylation rather than mutation that leads to disease.
Comment: This is small study, but provides very interesting insight into a possible role for epigenetic changes in heart failure. The researchers now hope to identify ‘hotspots’ in the genome to help identify those people at greater risk of developing heart disease, and in particular those people at greatest risk of developing heart disease rapidly. This would allow treatments to be targeted to those at greatest risk, and also enable closer monitoring of those at higher risk, to help prevent and delay heart failure.