Genetic Variant Conferring Resistance to African Sleeping Sickness Linked to Kidney Transplant Function
The parasite that causes African sleeping sickness, among red blood cells
The organs in the human body normally do their many jobs without complaint, but sometimes, whether it’s due to disease or injury, an organ fails and needs to be replaced with a healthy one from a donor. Although organ transplants are often successful, they come with many risks, too: the recipient’s body may reject the donor organ, and medications used to reduce the possibility of rejection suppress the recipient’s immune system to the point that he or she may be susceptible to dangerous infections. On top of all that, the donated organ itself may fail. Because of these possible serious complications, doctors and transplant centers invest a lot of effort to match recipients to potential donors from the limited pool of donors available.
Although many organs can now be transplanted, kidneys are by far the most transplanted organs. In 2010, nearly 17,000 kidneys were transplanted in the United States compared to just over 6,000 livers, the second most commonly transplanted organ. Despite these numbers, kidney transplants still suffer from the same possible complications as other organ transplants. In addition, studies in the last 10 years have found that kidneys donated by African Americans function for shorter periods of time than kidneys donated by European Americans, regardless of recipient ethnicity but for unknown reasons. A recent study published in the American Journal of Transplantation sheds some light on this mysterious phenomenon.
In this study, researchers studied kidney graft survival in 136 recipients from 106 African American donors. They found preliminary evidence to suggest that kidneys from donors (without detectable pre-existing kidney disease) who carry two copies of variants in the APOL1 gene survived for shorter times than kidneys from donors carrying one or no copies. There is evidence that the same variants are also associated with non-diabetic kidney disease in African Americans. The authors of this study suggest that kidney donors with two copies of these risk variants may have had undetectable kidney disease that led to shorter kidney survival time after transplant. Although the association with kidney transplant function is preliminary, this work suggests new ways in which genetic variants may influence the chances of transplant success and aid in the refinement of the organ matching process.
While it may not seem beneficial to have a variant that predisposes to kidney disease and reduces kidney transplant survival, researchers suggest that variants in the APOL1 gene may have evolved for similar reasons as the variant that causes sickle cell disease (which confers resistance to malaria in those carrying one copy of the variant). The ApoL1 protein is toxic to the parasite that causes African sleeping sickness, but new strains of the parasite have evolved that can tolerate the protein. It turns out that genetic variants in APOL1 associated with kidney disease also lend resistance to one of these new strains of the African sleeping sickness parasite. These variants occur only in populations where sleeping sickness is prevalent.
