Millions with Genetic Variant Raising Risk of ‘Implosive’ Cell Death

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A team of researchers has identified a genetic issue that takes the cellular brakes off necroptosis – the type of programmed cell death that usually alerts the immune system to the presence of invaders. However, it can trigger an excessive inflammatory response if uncontrolled.

In the latest study, researchers estimate that this genetic variant, a single-base change in the gene encoding a protein called MLKL, can be found in up to 3 percent of people. That amounts to millions of people worldwide.

Furthermore, the researchers didn’t associate this MLKL gene variant with any one particular disease, though after characterizing its effects in cell cultures and animal models, They claimed it could increase people’s risk of inflammatory diseases such as diabetes, especially when combined with other genetic and environmental factors.

Cells die all the time in our bodies in different ways. Many of these deaths happen without much fanfare. Other deaths happen under duress of an infection self-implode. Their disintegrated remains trigger the immune system into a state of heightened vigilance.

Two things can cause problems in the human body. One is that cancer can occur if cells don’t die. The second is that unleashing too much inflammation can occur if cells go boom more often than they should.

For most humans, the MLKL will stop when the body tells it to stop, but 2 to 3 percent of people have a form of MLKL that is less responsive to stop signals. That statement is from Sarah Garnish, a cell biologist at the Walter and Eliza Hall Institute of Medical Research (WEHI) in Melbourne, Australia. She is part of the latest study.

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She said this adds up to many millions of people carrying a copy of this gene variant when the number is considered globally.

The latest study has been published in Nature Communications.

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