New hope for Raynaud’s treatments after researchers confirm genetic causes

Until now, little has been known about why Raynaud’s develops. It is a painful and chronic condition that affects blood circulation in the body’s extremities, such as hands, feet, nose and ears, and can develop at any age. There are limited treatment options and no cure.  

These new findings not only add to our understanding of the condition but will hopefully lead to more effective treatments for people with the condition. 

Commenting on the research, Dr Emma Blamont, Head of Research for SRUK, said: "Raynaud's is a painful, chronic condition that affects around one in six people in the UK. We know that attacks can be brought on by certain triggers like cold and stress, but relatively little is known about why some people experience Raynaud’s and others don’t. For the millions of people living with this condition, simple everyday tasks can be a challenge, so research like this, which significantly advances our understanding of Raynaud's and the role that genetics may play in causing it, is crucial. 

“The next step is to confirm these important findings in more diverse population groups and validate the results through functional studies. If successful, these findings could help us unlock more new therapeutic avenues for Raynaud’s leading to better, more targeted and kinder treatments." 

The genetic causes of Raynaud’s 

Raynaud’s affects around 10 million people in the UK. It causes painful ‘attacks’ where the blood temporarily stops flowing to parts of the body, most commonly the hands and feet, in response to cold temperatures and stress. 

To investigate why this happens, scientists from Queen Mary University of London’s Precision Healthcare Research Institute (PHURI) and the Berlin Institute of Health (BIH) at Charité – Universitätsmedizin Berlin carried out the largest-ever study to identify genetic variants associated with the condition.  

The team analysed the electronic health records of more than 5,000 people living with Raynaud’s. They discovered that a variation in two genes increased the likelihood of a person developing the condition. 

• the alpha-2A-adrenergic receptor for adrenaline, ADRA2A, a classic stress receptor that causes the small blood vessels to contract 
• The IRX1 gene, which is thought to regulate the ability of blood vessels to contract.  

Professor Maik Pietzner, Health Data Chair of PHURI and co-lead of the Computational Medicine Group at BIH explained: “[The ADRA2A] receptor seemed to be particularly active, which could explain the vasospasms, especially in combination with the second gene that we found.”  

“If [the production of IRX1] is increased, it may activate genes that prevent constricted vessels from relaxing as they would normally do. Together with the overactive adrenaline receptor, this may then lead to the vessels not supplying enough blood for a longer period of time, which leads to the observed white fingers and toes.” 

These findings also help us to understand for the first time why small blood vessels react so strongly in patients, even apparently without external stimuli, such as exposure to cold. 

For their research, the team sourced health records from UK Biobank, a large-scale biomedical database and research resource, and Queen Mary’s Genes & Health study. The researchers were also able to replicate parts of their findings using data from participants of British Bangladeshi and Pakistani origin from the same Queen Mary’s study.  

The researchers’ findings have been published today in the highly regarded scientific journal Nature Communications. 

What the research means 

Ultimately, we hope this knowledge will lead to better treatments for Raynaud’s.  

Currently, there are limited options available; doctors usually advise patients on ‘self-help’ strategies to avoid triggering attacks. In severe cases, medications can be prescribed, but these are 'repurposed drugs' - originally developed to treat another condition – and often aren’t suitable for everyone. 

By understanding the underlying genetic mechanisms that cause Raynaud’s, researchers can begin to develop targeted treatments, and identify other existing drugs that may also be effective. 

Professor Claudia Langenberg, Director of PHURI, said: “I am convinced that our findings provide a path to novel effective medications. For example, already approved drugs that more or less specifically inhibit the function of ADRA2A could be an alternative, such as the antidepressant mirtazapine.” 

Visit our Raynaud’s information pages to learn more about the condition, including diagnosis, treatments and ways to manage it.