Raynaud’s syndrome, characterized by sudden pallor in the fingers and toes, is a perplexing vascular disorder. This condition is driven by spasms in the small blood vessels, disrupting skin circulation and potentially causing discomfort. While exposure to cold is a common trigger, emotional stress can also induce these vasospasms.
Remarkably, 2 to 5 percent of the population inherit this condition. Despite its relatively high prevalence, the genetic underpinnings of Raynaud’s syndrome have remained largely unexplored.
A Breakthrough in Genetic Research
To shed light on this enigma, Dr. Sylvia Hartmann and her team at the Berlin Charité conducted a genome-wide association study. They analyzed data from 5147 individuals with Raynaud’s syndrome and 439,294 healthy control subjects from the UK Biobank. This extensive analysis uncovered previously unknown genomic regions linked to the risk of Raynaud’s syndrome. These groundbreaking findings have been published in the prestigious scientific journal “Nature Communications.”
The Key Genetic Players
Notably, variations in two genes were strongly associated with an increased risk of this condition. The first is the α-2A adrenergic receptor for adrenaline, known as ADRA2A. This receptor is a classic stress receptor that mediates the constriction of small blood vessels.
Professor Dr. Maik Pietzner, Group Leader at the Berlin Institute of Health (BIH) in the Charité, explains, “This makes sense when it’s cold or dangerous because the body needs to supply the internal organs with blood. In Raynaud’s patients, this receptor seems to be particularly active, which could explain the vascular spasms, especially in combination with the second gene we’ve identified.” The second gene is the transcription factor IRX1, which may regulate the ability of blood vessels to dilate.
Unraveling the Mechanism
When the production of IRX1 is elevated, the constricted vessels struggle to relax promptly. This, in conjunction with the overactive adrenaline receptor, may result in prolonged periods of poor blood circulation, leading to the observed pallor in the fingers and toes.
A Ray of Hope: Therapeutic Avenues
In a quest for potential treatments, Dr. Hartmann’s team scoured the Open Target Database and identified 50 compounds with some affinity for ADRA2A. While there are already approved drugs that act antagonistically on the α2-Adrenoreceptor, such as the antidepressant Mirtazapin, these are not specific to this receptor and have, in some reported cases, worsened symptoms in Raynaud’s patients.
The possibility of systemic or topical treatment with Mirtazapin to alleviate vasospastic attacks in Raynaud’s patients remains a subject for clinical studies. In a prior investigation, the α2-adrenergic agonist Methyldopa showed promise in alleviating symptoms in Raynaud’s patients.
The genetic roots of Raynaud’s syndrome have been uncovered, offering a potential path to novel therapies. This discovery marks a significant leap forward in our understanding of the condition and brings hope for improved treatments for individuals living with Raynaud’s syndrome.
Original source: This information was Initially covered by PZ.de and has been translated for our readers.