Study finds clues to kidney disease in African Americans

African Americans are four times as likely to have kidney disease as Caucasians, and a recent study from Harvard University may explain why.

Nephrologist Martin Pollak and his team found that a common genetic mutation of the APOL1 gene might be partly responsible for African Americans' susceptibility.

The mutation likely arose due to natural selection because it protects against African sleeping sickness, Pollak wrote. Yet it also makes African Americans more vulnerable to kidney disease, according to the study released last month in the online issue of Science Magazine.

"This is clearly a landmark paper," says nephrologist Lawrence Holzman, chief of the Renal-Electrolyte and Hypertension division at the University of Pennsylvania. He estimates that African Americans make up 70 percent of his patients. "It's amazing how natural selection plays such an important role in a common disorder," Holzman said. "This will start a gigantic avalanche for kidney research."

Penn evolutionary geneticist Sarah Tishkoff also praised the work, calling this one of the most important examples of genetic variation since the discovery of the sickle cell trait, which protected against malaria.

Pollak's laboratory has recently designed a specific APOL1 test to detect the presence of the mutations. The researchers hope this mechanism will pinpoint those individuals who are at high risk for kidney damage.

"We need to figure out the mechanism by which these variants cause disease," Pollak said. "Then, we hope, we can start to think about treatment."

The Harvard researchers used DNA samples from the 1000 Genomes Project's database of individuals of African, European, and Asian descents. They discovered that 30 percent of African American chromosomes contained a mutated APOL1 gene, and observed that individuals with kidney failure were three times as likely to have both copies of the variant. Genetic alterations in other ethnic groups were not found.

APOL1 can work to inactivate Trypanosoma parasites that cause the sleeping sickness. However, it can be ineffective against highly toxic forms of the parasite.

Pollak and collaborators found that plasma from APOL1-mutated individuals was able to kill one of the most lethal parasites, Trypanosoma brucei rhodesiense. But plasma from other ancestral groups and African Americans without the gene variant had no effect.