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Gene Tied to Kidney Disease, Sleeping Sickness in African Americans

Posted Aug 02 2010 10:55am

Variants of a single gene may help protect against a sometimes-deadly parasite infection, but at the same time raise the risk for kidney disease in African Americans. The finding may eventually lead to better treatments for both conditions.

Scanning electron micrograph of a trypanosome parasite.
The parasite Trypanosoma brucei causes African sleeping sickness. Gene variants that help to protect against the parasite may also raise the risk for kidney disease in African Americans. Image by the Gull Lab, Sir William Dunn School of Pathology. All rights reserved by Wellcome Images.

Long-term kidney disease affects about 23 million adults nationwide. The disease hits the African American community especially hard, with rates up to 4 times higher than in European Americans. Two years ago, NIH-funded research teams reported that variations in or near a gene called MYH9 were associated with an increased susceptibility to kidney disease among African Americans. However, no specific MYH9 variants were definitively shown to raise the risk.

In the new study, an international team of scientists led by Dr. Martin Pollak of the Beth Israel Deaconess Medical Center took a closer look at the genetic regions in and around MYH9. The team included 3 NIH scientists. The research was funded in part by NIH's National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Cancer Institute (NCI) and National Heart, Lung and Blood Institute (NHLBI).

As reported in the July 15, 2010, early online edition of Science, the researchers did an initial analysis of nearly 400 African Americans. About half had a common type of kidney disease called focal segmental glomerulosclerosis, which can lead to kidney failure. The other half were healthy volunteers. A second analysis looked at a larger group of over 2,000 African Americans. About half had end-stage kidney disease.

The scientists found that 2 particular variants of a gene called APOL1 were strongly linked to both types of kidney disease. The gene encodes the protein apolipoprotein L-1 (ApoL1), a major component of HDL, or "good" cholesterol. People who inherited 2 copies of the variants—one from each parent—had a significantly higher risk of kidney disease than people who had only 1 or no variants.

Further analysis showed that the 2 APOL1 variants were most common in West African populations and in African Americans. The variants were not found in people with European, Chinese or Japanese ancestry.

Suspecting that the 2 gene variants might offer an evolutionary advantage to people in Africa, the scientists focused on a little-known function of the ApoL1 protein. It’s been shown to be involved in the body’s defense against parasites called trypanosomes, including Trypanosoma brucei, which causes African sleeping sickness. This degenerative and sometimes fatal disease affects tens of thousands of people in Africa but isn’t found elsewhere.

Laboratory tests showed that blood from patients who had variant forms of the ApoL1 protein destroyed the deadliest subtype of T. brucei. The researchers propose that APOL1 variants may have helped to protect Africans against this lethal parasite, which may explain why these variants are so common in certain African populations today.

"We were excited that our findings appeared to relate kidney disease in the United States with human evolution and parasite infection in Africa," says Pollak. "We hope that these new findings will not only lead us to a better understanding of the underlying mechanisms leading to kidney failure, but will also help us develop new ways to treat trypanosome infection and kidney disease."

—by Vicki Contie

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