Millions carry a gene mutation scientists just linked to inflammation

Scientists have found a gene mutation in a small but significant portion of the population, and using cells and mice models have found the mutation increases inflammation. If this is translated to humans it may raise the risk of inflammatory diseases like inflammatory bowel disease.

A team at WEHI in Melbourne discovered that 2-3% of the population have a gene mutation that could provide both ‘explosive’ cell death called necroptosis, and an increase in inflammation. While 2-3% of the population doesn’t sound high, around the world this could mean millions of people have the mutation.

“Programmed cell death is something that happens all the time, all over the body, millions and millions of cells are being cleaved by the body, and that’s really important,” says WEHI’s Dr Joanne Hildebrand, one of the researchers from the new study.

“We found that between 2-3% of people in the world carry a small change in one of their genes that is really important for programmed cell death. We think that particular change makes these people a little bit better at performing a form of programmed cell death called necroptosis.”

The biochemists had been studying a particular gene called MLKL, which is an important protein involved in necroptosis. While they don’t normally look at population genetics, they started looking into it after discovering a number of people with inflammatory diseases who had a particular mutation called p.Ser132Pro in the protein.

“I had a look at that mutation [inside a gene database] and went ‘oh my God, there’s so many people out there carrying this variant, I reckon it might be worth having a look to see if it does anything’,” said Hildebrand.

“And so, we made that same change in the mouse version of the gene.”

When the researchers looked at the gene in both human and mouse cells they found that the gene mutation caused more of the protein to accumulate, allowing a more ‘explosive’ necroptosis. But they also found that it increased inflammatory properties.

In mice models, the mutation made the mice less able to clear a salmonella infection, suggesting that although it causes more necroptosis, this likely not a beneficial mutation.

“We want to know, what’s the point of having a gene change like this? Is it a good thing? Is that a bad thing?” says Hilderbrand.

“Because programmed cell death is so important to the immune system, our hypothesis is that somewhere in human history having this particular gene change made carriers more likely to survive in the event of a certain infection, whether it’s a viral infection or a bacterial infection.”

Researchers have released a paper published in Nature Communications investigating the potential link.

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