BIDMC logoWhile there is a likelihood of a kidney disease occurring in any individual, it has been claimed that most African Americans face a four times higher rate of kidney disease than European Americans. In fact, almost half a million people in the United States seemingly require dialysis treatments to replace the function of their failed kidneys. Experts from the Beth Israel Deaconess Medical Center (BIDMC) and the Universite Libre de Bruxelles supposedly unravel the genetic secret for elevated incidence of kidney disease among African Americans.

While conducting the study, the authors noted that patients with focal segmental glomerulosclerosis (FSGS) and hypertension-attributed end-stage kidney disease (H-ESKD) accommodated variants in the APOL1 gene that altered the APOL1 protein sequence. These variants are claimed to be usually identified in individuals of recent African ancestry. It was also mentioned that the disease-causing variants seems to have protected Africans against a lethal parasite. Therefore, these genetic variants are common in this population.

Martin Pollak, MD, Chief of Nephrology at BIDMC, Associate Professor of Medicine at Harvard Medical School and co-senior author commented, “We found that the APOL1 risk genes for renal disease occur in more than 30 percent of African-American chromosomes. In fact, the increased risk of kidney disease in individuals who inherited two copies of these variant forms of APOL1 is reported to be approximately 10-fold.”

The scientists elucidate that FSGS is a form of injury to the kidney’s filtering system. It causes protein loss into the urine and eventually decreases kidney function. In instances where kidney failure has progressed to the requirement of dialysis or kidney transplantation, the ailment is termed as ESKD, or end-stage kidney disease.

Pollak affirmed, “G1 and G2 both changed the coding sequence of APOL1. Further analyses revealed that these very same genetic variants [G1 and G2] conferred human immunity against the parasite responsible for sleeping sickness.”

Association on the genetic variation near the MYH9 gene on chromosome 22 and elevated risk of kidney disease in African-Americans was apparently identified in 2008. The location of the disease-causing genetic variants appears to be in a broader region because genome analyses had previously shown a strong signal of natural selection in the region containing the MYH9 and APOL1 genes. It is also anticipated that the frequency of these variants would be markedly different between European-Americans and Africans.

Pollak highlighted, “We were excited that our findings appeared to relate kidney disease in the United States with human evolution and parasite infection in Africa. While there are many details that remain to be clarified in future studies, we do know that sickle-cell disease is a well-established precedent for this model, in which one copy of the mutation confers protection against a parasitic infection but two copies of the mutation can cause severe disease.”

During the investigations, the authors accumulated data from the 1000 Genomes Project DNA data bank. This supposedly enabled investigators to discover the candidate genetic variants and further tested for their presence in DNA sample sets. It was concluded that two APOL1 variants G1 and G2 may be correlated with a heightened risk of both FSGS and hypertension-attributed ESKD in African-Americans.

Pollak said, “It appears that we may have found a similar situation in APOL1. Consequently, while these genetic variants protect against sleeping sickness, they also greatly increase a person’s susceptibility to kidney disease. 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.”

The tsetse fly apparently transmits an African trypanosome parasite which causes African Sleeping Sickness. It is known that this disease leads to extreme nervous system disorders that can eventually result in brain damage, coma and death. Although approximately tens of thousands of people seem to be affected with this disease, the ailment is not identified outside Africa.

The APOL1 protein which is believed to circulate in the blood aids in protecting against trypanosomes. The scientists noted that the patients harboring the G1 and G2 variants inactivated the trypanosomes. This may be the cause of the deadliest forms of African Sleeping Sickness. The APOL1 protein seems to follow the same with these similar variants inserted. While presence of some hemoglobin mutations in a single copy may defend against malaria, two copies can lead to sickle cell disease or thalassemia, severe red-blood cell diseases.

The study is published in the July 15 online issue of the journal Science.