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.
Like the sickle cell trait, the gene is recessive, Pollak explains. "Those who inherit one mutant APOL1 gene are resistant to African sleeping sickness, whereas those with two copies are at risk for renal failure," he said. The nephrology chief at Beth Israel Deaconess Medical Center in Boston says the risk is 10 times higher for individuals with two alleles (forms), compared to those with one.
Any new treatment from this research can't happen soon enough for West Philadelphia native Jeffrey B. Cooke Sr., 45, who learned he had kidney failure three years ago. Cooke represents the third generation of renal-failure victims in his family and is one of the 136,000 African Americans undergoing dialysis treatments across the country, according to the National Kidney Foundation.
"I always talk to my 10-year-old son," Jeffrey Jr., "about the importance of taking care of his body and watching what he eats," says the father of two.
Cooke says the disorder has been limiting. "I can't partake in summer league sports, travel, or work because of my dialysis treatments, which are three times a week," said the former Lincoln University outfielder and Merrill Lynch financial adviser.
When told about the study, Cooke said "it's a nice thought to know that maybe something is out there. . . . I don't wish kidney disease on anybody, especially not my kids. I'm glad that there is hope for them."