Epigenetic changes can explain rheumatism
A new study by researchers at Karolinska Institutet in Sweden and Johns Hopkins University School of Medicine in the US shows that so-called epigenetic changes in the DNA are involved in causing rheumatoid arthritis, and that these changes can be genetically predetermined. The paper, which is published in the scientific periodical Nature Biotechnology, sheds light on how risk genes can be expressed in disease and why some individuals are affected more readily than others.
Rheumatoid arthritis (RA) has been shown to be closely associated with the genes or parts of the genome (DNA) that are important to the immune defence. These ‘immunogenes’ are partly responsible for the body’s autoimmune reaction against its own organs and tissues, which in turn causes rheumatism and similar diseases. At the same time, earlier research has shown that the risk of developing rheumatic disease is strongly linked to environmental factors, such as smoking.
Epigenetic mechanisms can be seen as a link between heredity and environment, whereby the latter gives rise to epigenetic modifications of the former without changing the actual DNA sequence. One such epigenetic mechanism is methylation, a biological process that, put simply, involves methyl groups becoming either attached to or detached from certain parts of the DNA molecule. This mechanism is essential for ensuring that the right genes are active at the right times in different cell types, and it has long been known that the epigenetic ‘reading’ of the DNA can be influenced by disease, particularly cancer.
In the present study, the researchers have shown, not only that epigenetic changes to certain immune genes are associated with RA, but that some of them actually seem to mediate its genetic risk. The team analysed methylation and DNA sequences in blood cells from a large number of RA patients and healthy controls. After running the data through a new mathematical model to discover correlations, they found that methylation at certain places only occurred if a person had a particular variant of a gene, concluding that this methylation could be an intermediary of the genetic risk of the disease.
“This could explain why risk genes assert themselves and cause disease and why some people are affected more easily than others,” says Tomas Ekström, Professor of molecular cell biology at Karolinska Institutet’s Department of Clinical Neuroscience and the Center for Molecular Medicine (CMM). “An example of this would be the gene variant that was previously linked to the increased risk of RA amongst smokers. We’re currently looking into whether there’s an intermediary epigenetic link between heredity and environment as regards smoking and RA.”
The study was led by Professor Ekström in association with Professor Lars Klareskog, also from the CMM, and Professor Andrew Feinberg from the Center for Epigenetics at Johns Hopkins. It was financed with grants from AFA Försäkring insurance company, the Swedish Research Council, the European Research Council (ERC) and the Swedish Rheumatism Association.
Publication: ‘Epigenome-wide association data implicate DNA methylation as an intermediary of genetic risk in rheumatoid arthritis’, Yun Liu, Martin J Aryee, Leonid Padyukov, M Daniele Fallin, Espen Hesselberg, Arni Runarsson, Lovisa Reinius, Nathalie Acevedo, Margaret Taub, Marcus Ronninger, Klementy Shchetynsky, Annika Scheynius, Juha Kere, Lars Alfredsson, Lars Klareskog, Tomas J Ekström, and Andrew P Feinberg, Nature Biotechnology, online 20 January 2013.
For further information, please contact:
Professor Tomas Ekström
Department of Clinical Neuroscience, Karolinska Institutet
Tel: +46 (0)8-517 746 34 or +46 (0)739-82 36 11
Professor Lars Klareskog
Department of Medicine, Solna, Karolinska Institutet
Tel: +46 (0)8-517 745 29 or +46 (0)70 5227788
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Karolinska Institutet is one of the world’s leading medical universities. It accounts for over 40 per cent of the medical academic research conducted in Sweden and offers the country’s broadest range of education in medicine and health sciences. Since 1901 the Nobel Assembly at Karolinska Institutet has selected the Nobel laureates in Physiology or Medicine.