;Resize=(1200,627)&impolicy=perceptual&quality=mediumHigh&hash=0b2e8ef322e9c8a3d9ba17877bcb18c736e7594eda60c5be7b7bb8b968c52fe0 "Long-Covid: Researchers find risk gene variant – FOCUS online")
So far, science has assumed that long-Covid can affect anyone – regardless of age or the severity of the corona disease. However, researchers have now found a risk factor – and it lies in our genes.
For the first time, researchers have discovered a genetic risk factor that makes its carriers more susceptible to long-Covid. It increases the risk of long and post-Covid by 1.6 times, genome-wide association studies have found. The newly identified DNA segments are close to the FOXP4 gene, which is important for the function of alveoli and various immune cells and which also increases the risk of a severe course of Covid-19, as the scientists report in a preprint.
Why do some people develop long-lasting late effects after the acute coronavirus infection, while others do not? So far, this question has only been partially clarified. There is evidence that certain symptom combinations and protein biomarkers increase the later long-Covid risk. In addition, some epigenetic genome appendages of those affected appear to be changed in a characteristic way.
However, the underlying mechanisms of susceptibility to long-Covid and whether some of them may be genetic are open. To make matters worse, there are different forms and possibly also trigger mechanisms of Long Covid or Post-Covid.
Genome-wide comparative study
An international team led by Vilma Lammi from the Institute for Molecular Medicine in Finland may now have identified a first genetic risk factor for long-Covid. They tracked him down as part of a larger project that used genome-wide association studies (GWAS) to search for risk genes for severe courses of Covid-19. Lammi and her colleagues have now used some of this data to look for risk gene variants for long-Covid.
For their study, they compared the genomes of 6,450 people with Long-Covid and more than a million controls, some of whom were never infected with Corona, others who survived Covid-19 without consequences. The genetic data came from 24 studies in 16 different countries. In their analysis, the researchers examined whether certain gene variants were significantly more common in the long-COVID patients than in the two control groups.
Significant risk factor at the FOXP4 gene
The result: “We discovered a genome-wide significant association within the FOXP4 gene locus,” Lammi and her team report. In this DNA section on the sixth chromosome, several sequence variants occurred particularly frequently in the long-Covid patients. These variants were all in the immediate vicinity of the FOXP4 gene and increase the risk of long Covid by about 1.6 times, as the researchers determined.
In additional analyses, Lammi and her colleagues investigated in which cells the FOXP4 gene is active and what its function is. Accordingly, this gene is read in a number of tissues, including various lung cells. “We found the highest reading activity in type 2 alveolar cells, a cell type in the air sacs of the lungs that is involved in the lung’s immune response,” reports the team. The gene is also suspected of promoting scarring (fibrosis) of the lungs and airways.
In addition, the FOXP4 gene is also active in the mucous membranes of the digestive tract and in various defense cells of the immune system, including the killer T cells, the B cells and the regulatory memory T cells.
Effect on the immune system and lungs
These observations could suggest that the connection between FOXP4 and long-Covid goes back to both lung function and immunology,” Lammi and her colleagues state. This also fits in with the fact that this gene is already a risk factor for severe courses of Covid in the main study -19 was identified “However, the effect on long-Covid was stronger than one would expect from this vulnerability in acute Covid-19 disease alone,” explains the team.
According to the researchers, this suggests that the FOXP4 gene locus represents a genetic risk factor for Long Covid, which also increases the susceptibility to late effects independently of its effect on the acute infection. In addition, the identification of these risk variants now provides new evidence of the genetic mechanisms behind Long-Covid, according to the scientists. “Further studies will certainly increase the number of known risk variants and could then also help to further clarify the biological mechanisms behind Long-Covid.”
Von Nadja Podbregar