We’ve waited a long time for news of promising research on the cause of Raynaud’s. Finally, scientists recently reported they’ve discovered genes linked to Raynaud’s phenomenon.
Researchers at Queen Mary’s University and the Berlin Institute of Health carried out the largest genetic study of Raynaud’s phenomenon we’re aware of to date. The team used electronic health records from the UK Biobank containing genetic and health information from 500,000 U.K. participants to identify more than 5,000 people affected by Raynaud’s. This data was used to assess whether sufferers of Raynaud’s are genetically different from those not known to have the condition. The study was published in the journal Nature Communications.
Now, before we get too excited about the research, keep in mind that the sample of patients studied with an incidence of Raynaud’s — while large in its absolute number — represents only 1% of the full sample, yet we know that the incidence of Raynaud’s in the general population is estimated to be 5 times or more that number. So there may be some bias in the sample (e.g., unidentified cases), but still, this is a good start!
The study results show scientists identified two genes that predisposed participants to the primary form of Raynaud’s phenomenon: One was the alpha-2A-adrenergic receptor for adrenaline (ADRA2A). This receptor causes the small blood vessels to contract when the body senses stress or danger (think “Fight or Flight Response”).
The second gene is a DNA-binding transcription factor labeled IRX1 which regulates the ability of blood vessels to dilate. “If its production 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” explained professor Maik Pietzner, professor of health data modeling at PHURI and group leader at BIH who, along with professor Claudia Langenberg, led the study.
These findings of genes linked to Raynaud’s confirm what was learned in a 2012 research study conducted by Maqsood Chotani, a principal investigator at the Research Institute at Nationwide Children’s Hospital in Columbus, Ohio (New Raynaud’s Research on Alpha-2C Receptors). Dr. Chotani was quoted in that study as stating: “The alpha-2C receptor has a specialized role; in fact, we believe it is a stress-responsive receptor and in this case it’s actually conserving body heat,” he said. “So we know how the receptor is regulated in health. In disease — like Raynaud’s — there could be a dysfunction, there could be overactivity of the new players we have identified in this study.” This new research confirms his hypothesis.
And Dr. Chotani’s research confirmed an even earlier study a decade earlier conducted by Dr. Nicholas Flavahan at Ohio State University. His research focused on the body’s blood vessels and how they interact with norepinephrine — a chemical produced by the body to maintain blood pressure — and Alpha-2A receptors, proteins found on the surface of cells in the blood vessels. Dr. Flavahan stated that “our bodies continuously use norepinephrine and these receptor proteins to control blood flow and to maintain blood pressure.”
What Dr. Flavahan learned is that by preventing the interaction between norepinephrine and the Alpha-2C receptors, the skin’s blood vessels no longer constricted when exposed to cold temperatures. His research dates back to 2002 (Ohio State Research News: New Therapy Breakthrough).
Given this background, it’s frustrating to think that it’s taken decades to build on Dr. Flavahan and Dr. Chotani’s research, but we’re grateful to see it finally resurfacing with new findings.
Our hope is this recent study on genes linked to Raynaud’s will lead to more effective treatments. In the paper, professors Pietzner and Langenberg suggest that a widely used antidepressant drug called mirtazapine might be an option. We’ve heard over the years from patients taking antidepressants for other medical reasons that once they started on these drugs their Raynaud’s symptoms improved or even disappeared. This research may help explain these cases.
But before you ask your doctor to prescribe a drug like mirtazapine (brand name Remeron), keep in mind it can result in serious side effects, including confusion, drowsiness, weight gain, even potentially resulting in suicidal thoughts (that’s the black box warning on the package), so let’s wait and see where this latest research leads.
One additional caveat: We asked our Medical Advisory Board for a point of view on this study. They asked an important question that’s not published or reported with the research: What percentage of Raynaud’s patients have these genes? Why is that important? Because it tells you how many people with Raynaud’s this research can be applied to. An example provided by Dr. Thomas Lehman, one of the Raynaud’s Association’s Medical Advisors, states that there are certain genes that make you twice as likely to develop lupus, but less than five percent of lupus patients have those genes. And what if you only have one of them, not both? Still much to be learned…
Until we can answer some of these outstanding questions, we may unfortunately still feel left out in the cold, but at least we’re getting closer to a knowledge base that offers warmth to the millions of sufferers in the Raynaud’s community.
