03 October 2023 , 16:17
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One particular gene - known by the boffins as MLKL - is essential to triggering necroptotic cell death, which is a natural process that protects our body from infection. But in three per cent of the global population this can go wrong and trigger tissue damage.
A study led by Walter and Eliza Hall Institute of Medical Research (WEHI) could explain why some people have an increased chance of developing conditions like inflammatory bowel disease or suffer more severe reactions to infections.
Explaining where scientists hope the research will go, Dr Sarah Garnish said: "Every piece of information like this helps us make personalised medicine more of a reality.”Researchers have discovered variations in a gene that causes inflammation through a process called ‘explosive’ cell death.
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Gene variations make certain people more prone to inflammation (Getty Images/iStockphoto)Researchers hope this insight could lead to better personalised treatments for inflammation and other diseases.
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Cell death is an essential process that protects our body by removing unwanted, damaged or dangerous cells. WEHI's Dr Sarah Garnish, first author on the paper, explained that necroptosis, where the cells explode, sounds an alarm for other cells in the body to respond.
"This is a good thing in the case of a viral infection, where necroptosis not only kills the infected cells but instructs the immune system to respond, clean things up, and start a more specific, long lived immune response," Dr Garnish said.
"But when necroptosis is uncontrolled or excessive, the inflammatory response can actually trigger disease."
Usually when the body needs to trigger necroptosis, the gene MLKL applies the brakes so unnecessary cell damage doesn’t occur. But for three per cent of us this doesn’t quite happen.
Dr Garnish continued: "For most of us, MLKL will stop when the body tells it to stop, but 2–3 per cent of people have a form of MLKL that is less responsive to stop signals
"While 2-3 per cent doesn't seem like much, when you consider the global population, this adds up to many millions of people carrying a copy of this gene variant."
Scientists work to map the genome (Getty Images)The genetic changes combine with someone’s lifestyle, health history and wider genetic makeup to increase the risk of inflammatory diseases and severe reactions to infections.
Project leader Dr Joanne Hildebrand said: "Taking Type 2 diabetes as an example, it's rare that just one gene change determines whether someone will develop the condition.
"Instead many different genes play a role, as do environmental factors, like diet and smoking."
Dr Hildebrand added that it's not as simple as directly connecting this difference in the MLKL gene with the chance of someone developing inflammation.
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They said: "We haven't tagged this MLKL gene variant to any one particular disease yet, but we see real potential for it to combine with other gene variants, and other environmental cues, to influence the intensity of our inflammatory response."