Understanding gene-environment interactions in MS risk

03 March, 2015

Associate Professor Jeannette Lechner-Scott

Despite significant advances in treatment options for relapsing-remitting MS, the disease mechanisms remain unclear. MS is known to be autoimmune in nature, but what triggers disease onset is still not completely understood.

Associate Professor Jeannette Lechner-Scott, from the Hunter Medical Research Institute in Newcastle NSW, was recently awarded a three year project grant from MS Research Australia, to support her work identifying non-genetic risk factors that may be associated with vulnerability to MS.

Over the past ten years, a number of genetic and environmental factors have been associated with an increased risk of developing MS, including over 110 genetic variants, viral infections such as the Epstein-Barr virus, and other environmental factors (such as latitude and exposure to sunlight).

More recent research has been moving towards detailed investigation of the interaction between genes and the environment, known as epigenetics. The term ‘epigenetics’ describes a variety of external factors that influence the way DNA code is read by cells, without changing the actual DNA sequence. Associate Professor Lechner-Scott’s new study aims to examine the role of epigenetics in MS onset.

In an earlier study, her team isolated immune and blood cells from people with MS and healthy individuals, and looked for differences in one particular type of epigenetic change, called DNA methylation.

DNA methylation refers to the ‘bookmarking’ of DNA with chemical tags. This process helps to regulate the level of gene activity, by identifying which genes are switched on or off. Researchers can study the levels of DNA methylation and identify differences among individuals. DNA methylation can be modified by a variety of environmental factors, and therefore provides a connection, linking the influence of both genes and environment on health and disease.

Associate Professor Lechner-Scott’s research team discovered significant changes in the DNA methylation profiles of people with MS compared to healthy controls, and determined that the majority of these changes were clustered around one key region of DNA, a region which is known to regulate the immune system.

In this new project, the aim is to further study the changes identified in this region and assess what effect these changes might have on various features of MS such as onset, progression, and severity.

This study will be undertaken in collaboration with esteemed genetics researchers from around Australia. Co-investigators on the project include colleagues Professor Rodney Scott and Dr Rod Lea from the Hunter Medical Research Institute, Professor Helmut Butzkueven from the University of Melbourne, and Professor Bruce Taylor from the Menzies Institute for Medical Research in Tasmania.

This innovative study is one of the first methylation studies in MS. This type of epigenetics represents the next generation of genetic research – studying the non-genetic factors that influence the activity of genes and DNA.

The internationally respected team of researchers working on this study are key members of MS Research Australia’s ANZgene consortium which includes geneticists from around Australia and New Zealand. The ANZgene consortium has, since 2007, worked with international colleagues to completely change our understanding of MS.

Associate Professor Lechner-Scott also took part in the recent tenth anniversary celebrations of MS Research Australia, filming a mini-documentary where she discusses the momentous changes in the outlook and prognosis of MS over the past ten years.

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