New Australian research uncovers links between genetics, vitamin D and response to treatment

02 December, 2013
Recent Australian research conducted as part of the international effort, identified 48 previously unknown genes that affect the risk of developing MS, taking the total number to 110. This landmark paper represents the first stage of genetics research, which must then be followed up with analysis to determine ‘how’ genes act to change individual risk.

The current MS Research Australia Senior Research Fellow A/Professor David Booth at the Westmead Millennium Institute and his colleagues around Australia have been extremely busy tackling just this question. Their work has recently culminated in the publication of three papers in top scientific journals.

A/Professor Booth and the team used separate approaches to look at vitamin D genes, the interaction between genetics and treatment response, and to determine if an overall genetic signature can be used to predict the likelihood of MS.

The work has shown that the gene responsible for converting vitamin D to its active form, known as CYP27B1, behaves differently in different types of immune cells, depending which version of the gene is present. In particular, the version of the gene that confers MS risk is underactive in immune cells called tolerogenic dendritic cells, which are the cells that control the action of vitamin D on the immune system. The resulting effect appears to be a reduced ability to guard against autoimmune misfire.

The team also revealed how another gene, IL7Ralpha, may play a role in a person’s response to treatment. Using immune cells grown in the laboratory which contained different versions of the gene, the researchers showed that the cells responded differently to interferon beta treatment. Cells with the version of the IL7Ralpha gene that confers the highest risk of developing MS showed no response to interferon beta. This implies that correct signalling through the activity of this gene and its pathways is important in both the risk of developing MS and in the response to treatment with interferon beta. The group is now examining whether this information may be used clinically to assist treatment decisions for people with MS.

In the third project the team looked at the activity of a panel of genes in the blood of people with MS and healthy controls, and confirmed an earlier finding that the activity of these genes in blood represented a predictive ‘signature’ for MS susceptibility.

In the new study the team have refined this signature to a single gene called RPS6, which had higher activity in people with MS and showed that the gene activity varies by season, matching the monthly UV light index. They also showed that the RPS6 activity was reduced when people were treated with interferon beta. This exciting result means that RPS6 activity could also be used in the future to track the response to interferon beta treatment and assist with treatment choices.

‘Work such as this further defines MS susceptibility and helps identify people particularly likely to respond to certain therapies’, said A/Professor Booth, ‘Testing such possibilities is vital to developing cost effective therapies for autoimmune diseases’.

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