Raynaud syndrome is a condition that causes poor circulation and numbness in the extremities. One of the most common symptoms is pale fingers and toes in cold weather. Normally, in response to stress or cold temperatures, our blood vessels contract to preserve oxygen or heat. In people with Raynaud, this response goes too far, and they lose circulation. While some people do develop Reynaud in conjunction with other conditions, like autoimmune diseases, it isn’t quite clear what makes some individuals more susceptible. A new study looking at the genetics of Raynaud illuminates some of the underlying biology and genetics.
In this study, they compiled data from several different genetic biobanks, totalling over 1,000,000 people, 11,000 of which had Reynaud syndrome; they then looked for mutations that correlated with the condition. The mutation with the strongest correlation was in a gene called ADRA2A, which produces a protein that sits on the surfaces of muscle cells around blood vessels and activates in response to adrenaline. The researchers showed that when they increased the amount of the ADRA2A protein in these cells, low temperatures caused even more extreme contraction. There were also mutations in several other genes related to this specific pathway and another related to the immune system.
From these results, the researchers sketched out a mechanism for Raynaud syndrome, where misregulation of this signaling pathway leads to excessive response to adrenaline in the cold through ADRA2A. Fortunately, there are already drugs that target many of these genes, so clinical trials can start quickly to test their impact on Reynaud syndrome. The study left open the possibility of other pathways and immune function’s impact on Reynaud syndrome, which will hopefully be studied in the future.
This study was conducted by Anniina Tervi, a PhD student at the Institute of Molecular Medicine in Helsinki under Hanna Ollila, and Markus Ramste, a postdoctoral researcher in cardiovascular medicine at Stanford University.
Corresponding Author: Alex Yenkin
Press Article: “Raynaud’s Syndrome Genetics, Biology Uncovered in GWAS, Functional Study“, GenomeWeb
Original Article: “Genetic and functional analysis of Raynaud’s syndrome implicates loci in vasculature and immunity“, Cell Genomics
Image Credit: “Raynaud-Syndrome” by Niklas D is licensed under CC BY-SA 3.0