Gene Related to Multiple Sclerosis Explains Drug Side Effects

The biological role of a gene variant implicated in multiple sclerosis (MS) has been determined by researchers at Oxford University.

The finding explains why MS patients do badly on a set of drugs used successfully in other autoimmune diseases, such as rheumatoid arthritis and inflammatory bowel disease - something that has been a puzzle for over 10 years.

The study illustrates that understanding the details of how some changes in the DNA code are linked to common diseases can inform clinical practice and guide the treatments that people receive so as to prevent adverse side effects.

The Oxford University team, along with German, Danish and US colleagues, has published the findings in the journal Nature. They were funded through the MRC Human Immunology Unit, part of the MRC Weatherall Institute of Molecular Medicine, and the Wellcome Trust.

"The hope has been that analyses of the whole human genome would lead to findings that are clinically relevant," stated Professor Lars Fugger of the Nuffield Department of Clinical Neurosciences at Oxford University, who led the work. "We show that this is possible. It's one of the first such examples, certainly in autoimmune disease."

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Gene scientists in recent years have been successful at identifying hundreds of individual changes, slips and alterations in our DNA that can be reliably linked to the risk of many common diseases such as MS, diabetes and heart disease. But it has been difficult to determine which of these DNA changes are causal and what biological role they play in disease.

Besides, most of the gene variants only have small effects, each on their own accounting for little of the genetic contribution to disease. This has led some to question the worth of these very large genetic studies, or to suggest that the assumption that decoding the human genome would change medicine has been oversold.

"Some people say that genomic association studies haven't delivered on the promise of decoding the human genome"' says Professor Fugger. "But the postgenomic era has only just started."

The researchers investigated one particular genetic variant - found in a gene called TNFRSF1A - which has previously been associated with the risk of developing MS.

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Gene Related to Multiple Sclerosis Explains Drug Side Effects