In a genetic study of 2866 Danish children aged 0-6 years with severe asthma attacks, researchers from COPSAC in collaboration with researchers from DTU, SSI and several American research groups have been able to identify a new asthma gene called FUT2 as in interaction with the AB0 blood type increases the risk of childhood asthma and bacterial infections.
In the study, the researchers examined the genome of children with a particular type of asthma, characterized by severe asthma attacks in the first 6 years of life. By comparing the children’s genes with children without asthma, they could see that the children with asthma more often had special variants in a gene called FUT2.FUT2 determines whether the AB0 antigens are excreted on the mucous membranes of the body and in the mucus produced in the airways. Approx. 80% of all people of European ethnicity secrete the AB0 antigens, so-called “secretor status”.
The researchers then investigated whether there was an interaction between FUT2 and the children’s AB0 genes and found that this was the case. FUT2-secretor status was a risk factor in children who had A or B antigens, while it was not a risk in children with blood type 0. Similarly, it was only a risk factor to have A or B antigens for children who were also “secretors”. The results suggest that secretion of A and B antigens in the airways increases the risk of childhood asthma.
In addition to the study in the 2866 Danish children with severe asthma attacks, the researchers followed up the results in two Danish cohorts of children (COPSAC birth cohorts) and in an American cohort (COAST) and here they found that the underlying mechanism behind the increased asthma risk is related for specific infections with the bacterium S. pneumoniae, also called pneumococci. As with pediatric asthma, it was the combination of having FUT2 “secretor” status and a blood type with A or B antigens that gave the greatest risk of infections. The results are the first robust and biologically plausible example that the interaction between different genes is crucial in relation to the risk of childhood asthma.
Professor Klaus Bønnelykke, Copenhagen Prospective Studies on Asthma in Childhood, who has led the research project says: “The study helps us understand why some children develop childhood asthma and more often get respiratory infections. We hope that in the future this knowledge can be used for targeted prevention and treatment of childhood asthma. At the same time, the study shows that it is important to make studies of the sickest children who have severe asthma attacks despite medical treatment, because there may be other mechanisms at play in them. We are therefore now doing a national study of children with severe asthma to better understand their disease.”
The research has been supported by grants from Lundbeck Foundation, Børnelungefonden and Novo Nordisk Foundation.
FACTS
The scientific study will be published in Nature Communications on December 16, 2020. Read the article here.
Childhood asthma
Asthma is the most common chronic disease among children and at the same time the most common cause of hospitalization. Approximately 10 percent of Danish children of school age suffer from asthma, while 15-20 percent of children of toddler age suffer from asthmatic symptoms. The incidence of asthma in children has doubled in the Western world in recent decades without knowing why.
AB0
The gene AB0 determines one’s blood type (A, B, AB or 0) and thus which antigens one has. Antigens from the AB0 blood type system are found on all cells in the body. The system is characterized by two AB0 antigens, which are called A and B antigen, respectively. Type 0 has neither A nor B antigens, whereas type AB has both.
Contact
Professor Klaus Bønnelykke
Email. kb@copsac.com
Tel. +45 38677360