Researchers at Queen Mary University of London’s Precision Healthcare Research Institute (PHURI) and Charité – Universitätsmedizin Berlin’s Berlin Institute of Health (BIH) have made a potential breakthrough in the treatment of Raynaud’s phenomenon. The genetic causes of this disorder have been uncovered in a recent study published in Nature Communications, which could pave the way for the development of effective treatments.
Raynaud’s phenomenon (RP) is a heritable blood circulation disorder that affects approximately 2-5% of the population. It is characterized by vasospasms, where small blood vessels near the skin’s surface contract and restrict blood flow. This often leads to discomfort, changes in skin color, and in some cases, severe pain or ulcers, particularly in response to cold temperatures or emotional stress.
Despite being a common condition, Raynaud’s has been under-investigated, with little known about its genetic causes. Current treatment options are limited, focusing on self-management strategies such as keeping warm and avoiding triggers. In severe cases, medications that are typically used for lowering high blood pressure may be prescribed, but they often come with severe side effects.
To gain a better understanding of the genetic mechanisms underlying Raynaud’s phenomenon, researchers conducted the largest genome-wide association study (GWAS) to date. They analyzed electronic health records from the UK Biobank, which contains genetic and health information from half a million UK participants. By identifying over 9,000 individuals affected by Raynaud’s, the researchers discovered variations in two genes that predispose individuals to the disorder.
One of the genes identified was ADRA2A, which codes for the alpha-2A-adrenergic receptor for adrenaline. This receptor is responsible for causing small blood vessels to contract, and in Raynaud’s patients, it appeared to be excessively active. The researchers also found a link to the transcription factor IRX1, which may regulate the ability of blood vessels to dilate. When the production of IRX1 is increased, it can activate genes that prevent constricted vessels from relaxing as they normally would. The combination of an overactive adrenaline receptor and increased IRX1 production may lead to insufficient blood supply to the extremities, resulting in the observed symptoms of Raynaud’s.
The researchers were able to replicate parts of their findings using data from participants of British Bangladeshi and Pakistani origin, further supporting the significance of their discoveries.
Dr. Emma Blamont, Head of Research for Scleroderma and Raynaud’s UK (SRUK), emphasized the importance of understanding the genetic causes of Raynaud’s and the role they play in its development. With millions of people living with this painful condition, this research could open up new therapeutic avenues and lead to more targeted and effective treatments.
Further studies are needed to confirm these findings in more diverse population groups and validate the results through functional studies. If successful, this research could revolutionize the treatment of Raynaud’s and alleviate the challenges faced by individuals living with this condition on a daily basis.
