Genes Preventing a Deadly Illness Could Also Lead to Kidney Diseases


Some people have genes that provide resistance to a disease called sleeping sickness, which can lead to severe neurologic problems, and even death. Unfortunately, those same genes—which millions of African Americans carry—also make people more likely to develop chronic kidney diseases.

In a new study published in eLife, researchers present a new clue as to why the genes do this. Postdoctoral researcher Russell Thomson, Professor Jayne Raper (Hunter College, The Graduate Center), as well as Ph.D. graduate Joseph Giovinazzo and former undergraduate researcher Nailya Khalizova were authors on the study, which also suggests the development of pharmaceuticals to counteract the disease effects.

Sleeping sickness is carried by the tsetse fly of sub-Saharan Africa. Symptoms include severe headaches, fever, and fatigue, as well as more serious confusion, disturbed sleep patterns, and personality changes.

Humans have recently evolved two gene variants that work to protect against sleeping sickness, but people who have two copies of the variants in their genome are also more likely to develop chronic kidney diseases. Currently, an estimated 5 million African Americans carry two copies of the gene variants.

The researchers found that when a person has two copies, microscopic channels form in the membranes of their kidney cells. These channels allow sodium and calcium to enter the cells at toxic levels. Eventually, this toxic imbalance kills off the kidney cells.

While scientists have worked on this question before, different groups reached different conclusions. To address this, the authors looked for the earliest change caused by the gene variants—something that could explain the various effects observed later on.

Pharmaceutical efforts should focus on making small molecules to block these channels, the authors say, or preventing the channels from forming in the first place.