Oxford scientists find gene that doubles risk of dying from COVID-19
60% of people with South Asian ancestry carry gene known as LZTFL1, study finds
London: Scientists identified a specific gene that doubles the risk of respiratory failure from COVID-19 and may go some way to explaining why some ethnic groups are more susceptible to severe disease than others.
Researchers from the University of Oxford found that a higher-risk version of the gene most likely prevents the cells lining airways and the lungs from responding to the virus properly. About 60% of people with South Asian ancestry carry this version of the gene, compared with 15% of people with European heritage, according to the study published Thursday.
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The findings help explain why higher rates of hospitalisation and death may have been seen in certain communities and on the Indian subcontinent. The authors cautioned that the gene cannot be used as a sole explanation as many other factors, such as socioeconomic conditions, play a role. Despite a significant impact from the virus to people with Afro-Caribbean ancestry, only 2% carry the higher-risk genotype.
How the gene changes the way lungs respond
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. The finding, published in the journal 'Nature Genetics' on Thursday, could also partly explain the impact of COVID-19 in the Indian subcontinent. 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 COVID-19 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. 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. — PTI
People with the gene, known as LZTFL1, would particularly benefit from vaccination, which remains the best method of protection, the authors said. The findings raise the possibility of research into treatments specific to patients with this gene, though no tailored drugs are currently available.
This “shows that the way in which the lung responds to the infection is critical,” said James Davies, co-lead author and associate professor of genomics at Oxford, who worked in intensive care during the pandemic. “This is important because most treatments have focused on changing the way in which the immune system reacts to the virus.”
Davies and his colleagues found the gene using artificial intelligence and cutting-edge molecular technology. The team trained an algorithm to analyze large quantities of genetic data from hundreds of types of cells all over the body, and then used a new technique that allowed them to hone in on the DNA behind this specific genetic signal.
All other things being equal, “if you have the higher-risk genotype and you get very unwell with Covid, there’s a 50% chance that that wouldn’t have happened to you had you had the lower-risk genotype,” Davies said on a briefing with reporters Thursday.
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