Scientists at the University of Oxford have identified a gene that may double the risks of lung failure and death from COVID-19, and could explain why people of South Asian ancestry have a higher risk of severe disease.
The LZTFL1 gene changes the way the lungs respond to viral infection, and is the most important genetic risk factor identified so far, the researchers said.
They noted that the gene version is carried by nearly 60 per cent of people with South Asian background, compared with 15 per cent of those with European lineage.
The finding, published in the journal Nature Genetics on Thursday, could also partly explain the impact of COVID-19 in the Indian subcontinent.
Role of LZFTL1
The researchers used a combination of artificial intelligence (AI) and new molecular technology to pinpoint LZTFL1 as a gene responsible for the increased risks. LZTFL1 blocks a key protective mechanism that cells lining the lungs normally use to defend themselves from the viral infection, they said.
When these cells interact with SARS-CoV-2, which causes COVID-19, one of their defence strategies is to turn into less specialised cells and become less welcoming to the virus.
This process reduces the amount on the surface of cells of a key protein called ACE2, which the coronavirus uses to attach itself to the cells.
However, for people with the LZTFL1 gene this process does not work as well, and lung cells are left vulnerable to infection by the virus.
The researchers noted that it is particularly important to offer vaccination to communities that are at greater risk of serious Covid-19 infection as a consequence of carrying this genetic predisposition, as their increased risk should be cancelled out by immunisation.
Independent experts said the findings are very important but warrant further investigation.
“The discrepancy between the risk of serious disease and death in different ethnic groups has previously been attributed in part to socio-economic differences, but it was clear that this was not a complete explanation,” said Professor Frances Flinter, from Guy’s & St Thomas’ NHS Foundation Trust, UK.
“Evidence that LZTFL1 has emerged as a candidate causal gene, which is potentially responsible for some of the two-fold increased risk of respiratory failure from Covid-19 in some populations, provides a big step forward in our understanding of the variable susceptibility of some individuals to serious disease and death,” Flinter, who was not involved in the study, added.
Simon Biddie, from the University of Edinburgh, UK, said the study provides compelling evidence to suggest roles for LZFTL1 in severe Covid-19 that warrants urgent further investigation. “The finding will need further experimental verification to provide direct evidence for regulation of LZTFL1, using for example genome engineering approaches,” Biddie, who was not a part of the study, added.