Blame fainting on this gene

Researchers have identified a gene associated with an increased risk of fainting.

Heat, dehydration, and anxiety can cause people to faint, which has the potential to be fatal if it happens while driving or cycling. Now researchers have come closer to explaining the phenomenon.

The researchers analyzed data from the UK Biobank containing information on approximately 400,000 Britons. Out of the 400,000, 9,163 Britons had been in contact with the health care system due to fainting. To identify the genetic variants associated with fainting, the researchers systematically analyzed millions of genetic variants in the participants’ genomes.

“We have learned that a part of chromosome 2 increases the risk of fainting. This means that there is a genetic risk variant that predisposes to fainting. In addition, we are the first to show that fainting is genetically determined by linking an increased risk of fainting with an exact position in the genome,” says Morten Salling Olesen, an associate professor in the biomedical sciences department at the University of Copenhagen and the Laboratory for Molecular Cardiology at Rigshospitalet.

All of us have 23 chromosome pairs—or a total of 46 chromosomes in each cell. The genetic variant the researchers identified is on chromosome 2. A person can have one, two, or no risk variants on chromosome 2. Statistical calculations show that if the risk variant is found on both versions of chromosome 2, the person in question has a 30 percent higher risk of fainting compared to persons with none of the two variants.

Subsequent analyses have shown that the risk variant for syncope determines the extent to which a particular gene on chromosome 2 is expressed. The researchers believe that this misregulation of the gene is probably what increases the risk of fainting.

fainting graph
The researchers have shown that persons with two risk variants have the greatest risk of fainting (black curve), while persons with only one risk variant have a medium risk (red curve) and those with none of the risk variants have the lowest risk of fainting (green curve). (Credit: U. Copenhagen)

The researchers have also analyzed data from a Danish cohort of 54,656 individuals called iPSYCH from Statens Serum Institut. The result confirmed their previous findings. The researchers found the same genetic risk variant among the participants who had experienced fainting as in the British cohort. They discovered that women under the age of 35 faint approximately twice as often as men under the age of 35, but the cause is still unknown.

“In the study we show that if you are a woman and you carry the risk variant on both chromosomes on chromosome pair number 2, you have an approximately three times increased risk of fainting compared with men not carrying the risk variant. Your gender and a single genetic variant in your genome reveal a substantial part of your risk of fainting,” says Olesen.

The common belief is that fainting is caused by shortage of blood and oxygen to the brain, which results in short-term, total loss of consciousness. There are various types of syncope, the most frequent being vasovagal syncope. Here, a reflex—e.g. triggered by the sight of blood—causes significant lowered blood pressure conditioned by a slow heart rate and a dilation of the blood vessels leading to reduced flow of blood to the brain and fainting.

Between 20 and 30 percent of the population is believed to faint at least once in their lifetime. The gene the researchers identified to associate with fainting or syncope is called ZNF804A. They still do not know precisely which type of syncope the gene predisposes people to.

“This gene probably affects some of the reflexes that determine whether you faint or not. The question is whether the hereditary component is the same for all types of syncope. We believe that the gene we have identified predisposes to vasovagal syncope, which is the most common type of syncope. But we still do not know. First we need to study the gene in detail,” says Morten Salling Olesen.

Funding for the research came from the John and Birthe Meyer Foundation, Arvid Nilsson’s Foundation, the Novo Nordisk Foundation, Rigshospitalet’s research funding and the Research Committee, Rigshospitalet’s Heart Centre.

The research appears in the journal Cardiovascular Research.

Source: University of Copenhagen