Gene of the Month – November: LZTFL1

A gene variant in LZTFL1 is probably responsible for a twofold increased risk of dying of COVID-19. This has been found by British scientists at the University of Oxford. Using a machine learning approach, they analyzed data from several large genome-wide association studies which had previously revealed an associated stretch of DNA on chromosome 3. Now the scientists uncovered LZTFL1 as a candidate gene for increasing the risk of respiratory failure from COVID-19. Further molecular genetic analyses and investigations in cell models provided insights into the gene’s function.

The identified variant affects a so called enhancer, a DNA region that acts like a switch regulating how genes are expressed, and thereby increases the function of the leucine zipper transcription factor-like 1 protein. LZTFL1 has not been very well studied so far, but the results of the recent study show that it is produced in epithelial cells of the respiratory tract and is associated with lung function. The researchers found that the high-risk variant, which is present in 15 % of people of European ancestry and in more than 60 % of people with South Asian ancestry, causes increased inhibition of the cells’ proper response to infection. With these results, published in Nature Genetics, the study raises the possibility that LZTFL1 could be a potential target for the treatment of COVID-19.

Downes DJ, Cross AR, Hua P, … Hughes JR. Identification of LZTFL1 as a candidate effector gene at a COVID-19 risk locus. Nat Genet. 2021 Nov;53(11):1606-1615. doi: 10.1038/s41588-021-00955-3. Epub 2021 Nov 4.

Article in PubMed

Gene of the Month – November: LZTFL1

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