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Restless legs syndrome: new genetic clues may generate treatments

A new study, published in the scientific journal Nature Genetics on June 5, has discovered genetic clues that may be related to the causes of restless legs syndrome , a condition characterized by tingling, discomfort and an uncontrollable need to move the legs. The findings could help identify people at higher risk of developing the disease and point to possible new forms of treatment.

Restless legs syndrome is described as a movement-related sleep disorder in the International Classification of Sleep Disorders (ICSD3). Despite being relatively common — one in 10 elderly people have symptoms, with 2 to 3% of them being seriously affected — its causes are still unknown.

There are factors that are related to the emergence of the syndrome, such as depression, anxiety, cardiovascular diseases, hypertension and diabetes. Previous studies have already identified 22 genetic risk loci (regions of the genome that contain changes associated with an increased risk of developing the disease). However, there are still no known “biomarkers”, such as genetic characteristics, that can be used to diagnose the disease.

Therefore, researchers from the Helmholtz Institute for Neurogenomics in Munich, the Institute of Human Genetics at the Technical University of Munich (TUM) and the University of Cambridge gathered and analyzed data from three genome-wide association studies.

These studies compared the DNA of patients with restless legs syndrome and healthy individuals to see if there were differences between the two groups. By combining the data, the team was able to create a set of information from more than 100,000 patients affected by the condition and more than 1.5 million healthy people.

“This study is the largest of its kind on this common – but little understood – condition. By understanding the genetic basis of restless legs syndrome, we hope to find better ways to manage and treat it, potentially improving the lives of the many millions of people affected around the world,” says Steven Bell, study co-author and researcher at the University of Cambridge, in a press release.

Research findings could help develop treatments

A search identified more than 140 new genetic risk loci for restless legs syndrome, an eightfold increase from the previously known number to 164, including three loci on the X chromosome. Researchers found no genetic differences between men and women, although the The disease is twice as common in women, suggesting a complex interaction between genetics and hormones.

On the other hand, research has identified two genetic differences that involve genes known as glutamate receptors 1 and 4, important for nerve and brain function, respectively. According to the researchers, these genes could be targets of existing drugs, such as anticonvulsants (perampanel and lamotrigine), or could be used to develop new drugs for the syndrome.

Additionally, researchers believe it would be possible to use basic information such as age, sex and genetic markers to accurately classify who is most likely to have severe RLS in nine out of ten cases.

“For the first time, we have achieved the ability to predict the risk of restless legs syndrome. It has been a long journey, but now we are able not only to treat, but even to prevent the appearance of this condition in our patients”, says Juliane Winkelmann, professor at TUM and one of the senior authors of the study.

Source: CNN Brasil

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