Variations of the APOL1 gene may be associated with an increased risk of kidney disease, a finding that could help explain why the most serious forms of the disease are so common among African-Americans, a study reported.
The reason many African-Americans develop chronic and end-stage kidney disease may be that almost all have the G1 and G2 variations of the gene, University of Pennsylvania researchers said.
“Now that we know that the G1 and G2 mutated APOL1 proteins cause human-like kidney disease, we can start to look for ways to target them to reduce kidney disease risk among millions of people of African descent,” the senior author of the study, Dr. Katalin Susztak, said in a press release.
To prove the two variations can lead to kidney disease, researchers used a mouse model to trigger the expression of different variations of the human APOL1 gene in different cells.
The study, “Transgenic expression of human APOL1 risk variants in podocytes induces kidney disease in mice,” was published in the leading scientific journal Nature Medicine.
When the G1 and G2 variations were expressed in kidney filtering cells, the mice developed a kidney disease similar to the human disease at the functional, structural, and molecular levels.
“These mutant proteins caused the kidney filter to become leaky and scarred, resulting in defective kidney function,” Susztak said.
Further experiments revealed that the G1 and G2 variations encode for a protein that interferes with the filtering cells’ waste removal, resulting in inflammation and cell death. Because filtering cells can’t be renewed, their loss causes kidney tissue scarring that leads to chronic kidney disease.
Importantly, the researchers were able to reverse the development of the disease in the mice by turning off the expression of the G1 and G2 variations. Moreover, they found that the severity of kidney disease in humans they examined correlated with the level of G1 and G2 protein expression in their tissues.
Scientists think the reason why the seemingly harmful variations of the APOL1 gene are so common among people of African descent is that they help ward off the parasite Trypanosoma brucei, which causes African sleeping sickness. People with these variations are more likely not to get infected with the parasite and to pass on the gene to their offspring.