Variants linked to Kidney Disease in African-Americans

A team of researchers, including those associated with the Broad Institute, have come upon what they believe explains the increased risk of kidney disease found in African Americans.  In a Science journal paper published online July 15, investigators identified two variants of the ApoL1 gene located on chromosome 22 that are found in higher frequency in African-Americans with kidney disease. African Americans with two copies of either of these variants, known as G1 and G2, appear to have a 10-fold increased risk for kidney disease.

They also showed having one of these variants is protective against African trypanosomiasis (aka African Sleeping Sickness), a disease caused by infection from parasites of the Trypanosome family.  Co-author Etienne Pays found that individuals with the G1 or G2 variant in ApoL1 retain their ability to kill the parasite. Those without them are more likely to develop infection and trypanosomiasis.

The authors believe evolutionary pressure acting on these variants made them more common in people of recent African ancestry.

I interviewed Broad Associate Member Martin Pollak, MD, Chief of the Division of Nephrology at Beth Israel Deaconness Medical Center, and a co-author of the paper.  He explains that the idea to study ApoL1 and its link with kidney disease in some depth stemmed from another Broad-related project – the 1000 Genomes Project. The Broad is a major contributor in cataloging and contributing to the dbSNP database as a result of work from the 1000 Genomes Project and others. (To learn more about the 1000 Genomes Project see our latest news story on the effort.) The database serves as a public, central repository of SNP-related discoveries.

Other groups had previously shown that the region of chromosome 22 contained a kidney-disease susceptibility region. Pollak and colleagues performed a genome-wide analysis (GWAS) comparing African Americans with European Africans to identify any SNPs in the area of ApoL1. From their GWAS, they determined that the region contributing to kidney disease susceptibility might be bigger than originally suspected. “That led us to go through the publicly-available 1000 Genomes Project data looking for variants in this region of the genome that were very different in frequency between Europeans and Africans,” says Pollak. G1 and G2 were among those variants found in individuals with African ancestry.

This story is similar to the selective pressure on genes linked with sickle-cell disease. Individuals with two copies of a hemoglobin mutation get the disease while those with only one copy do not and are beneficially resistant to contracting malaria. 

But the story isn’t complete. “We need to make the biological connection between why people with these variants in the ApoL1 gene get more kidney disease,” according to Pollak. If the research continues to highlight these and similar variants, this could be an enticing new avenue of research for those working in kidney disease.