Navigation Links
Investigators identify gene associated with kidney disease in African-American population
Date:7/19/2010

WINSTON-SALEM, N.C. Monday, July 19, 2010 Kidney disease is a growing public health problem, with approximately half a million individuals in the United States requiring dialysis treatments to replace the function of their failed kidneys. The problem is particularly acute among African-Americans, whose rates of kidney disease are four times higher than those of European Americans.

As reported online this month by the journal Science, collaborating research groups found that patients with focal segmental glomerulosclerosis (FSGS) and hypertension-attributed end-stage kidney disease (H-ESKD) harbored variants in the APOL1 gene that changed the ApoL1 protein sequence. These variants are commonly found in individuals of recent African ancestry.

Furthermore, in a twist of evolutionary medicine, the disease-causing variants may have protected Africans against a lethal parasite, explaining why these genetic variants are so common in the population today.

Researchers at Wake Forest University Baptist Medical Center contributed to and participated in this scientific team, led by investigators at Beth Israel Deaconess Medical Center (BIDMC) and the Universite Libre de Bruxelles. Together, they discovered a genetic explanation with evolutionary roots for the higher incidence of non-diabetic kidney disease in African-Americans.

"We found that the APOL1 risk genes for renal disease occur in more than 30 percent of African-American chromosomes," explained co-senior author Martin Pollak, M.D., chief of nephrology at BIDMC and associate professor of medicine at Harvard Medical School. "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."

FSGS is a form of injury to the kidney's filtering system, which causes proteins to be lost into the urine and gradually reduces kidney function. ESKD, or end-stage kidney disease, is defined by kidney failure that has progressed to the point that the patient requires dialysis or kidney transplantation.

"It has long been thought that high blood pressure is a common cause of end stage kidney disease in African-Americans," said study co-researcher Barry Freedman, M.D., John H. Felts III Professor and chief of the section on nephrology at WFUBMC. "However, the strong association between variants in the APOL1 gene and hypertension-attributed kidney disease suggested that this kidney disease truly resides in the spectrum of FSGS and is not due to hypertension as was initially believed."

More than 2,000 study participants from the southeastern United States were recruited to the study by WFUBMC.

Last year, Freedman led a team of WFUBMC researchers who found that genetic variation near the MYH9 gene on chromosome 22 was also associated with increased risk of hypertension-attributed kidney disease in African-Americans. However, because genome analyses had shown a strong signal of natural selection in the region containing both the MYH9 and APOL1 genes, the authors reasoned that the location of the disease-causing genetic variants was in a broader region. They also predicted that the frequency of these variants would be markedly different between European-Americans and Africans.

Using data from the 1000 Genomes Project DNA data bank, the authors identified candidate genetic variants and tested for their presence in DNA sample sets. They found that two APOL1 variants dubbed G1 and G2 were associated with an increased risk of both FSGS and hypertension-attributed ESKD in African-Americans.

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

African sleeping sickness is caused by an African trypanosome parasite, which is transmitted by the tsetse fly. The disease, which produces severe nervous system disorders that can ultimately lead to brain damage, coma and death, is estimated to affect tens of thousands of people, but is not found outside of Africa.

The APOL1 protein circulates in the blood and helps defend against trypanosomes, a finding initially discovered by co-senior author Etienne Pays, Ph.D., of the Universite Libre de Bruxelles, in Belgium. In the current study, Pays' laboratory found that the plasma from patients harboring the G1 and G2 variants inactivated the trypanosomes that cause the deadliest forms of African Sleeping Sickness, as did the APOL1 protein with these same variants inserted.

"We were excited that our findings appeared to relate kidney disease in the United States with human evolution and parasite infection in Africa," Pollak said. "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." Pollak explained that, when present in a single copy, certain hemoglobin mutations protect against malaria. But two copies cause sickle cell disease or thalassemia, severe red-blood cell diseases.

"It appears that we may have found a similar situation in APOL1," Pollack added. "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."


'/>"/>

Contact: Jessica Guenzel
jguenzel@wfubmc.edu
336-716-3487
Wake Forest University Baptist Medical Center
Source:Eurekalert

Related medicine news :

1. Damon Runyon Cancer Research Foundation awards $3.1M to 8 top young clinical investigators
2. UT Southwestern investigators perform head-to-head comparison of incontinence treatments
3. Investigators examine colorectal cancer screening methods among diverse populations
4. Scientists identify natures insect repellents
5. U-M researchers identify gene mutation that causes rare form of deafness
6. Researchers identify factors behind blood-making stem cells
7. Diagnostic blood test can identify rare lung disease
8. Researchers identify key enzyme in melanoma cell development
9. Non-melanoma skin cancer may help identify survivors at increased risk for future cancers
10. Gene pattern may identify kidney transplant recipients who dont need lifelong anti-rejection drugs
11. Gene pattern may identify kidney transplant recipients who dont need life-long anti-rejection drugs
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:4/28/2017)... SALT LAKE CITY, UTAH (PRWEB) , ... April ... ... Josée Côté as Account Manager for the North East region. Côté has 20+ ... operations and consulting. Prior to Phytomer, Côté worked with an array of high-end ...
(Date:4/28/2017)... ... April 28, 2017 , ... Rob Lowe is a popular actor that has ... presence to an educational purpose as the host of the “Informed” series. The program ... a recent episode, the series focuses on thyroid cancer. , Although thyroid cancer is ...
(Date:4/27/2017)... , ... April 27, 2017 , ... ... Insights in Incentives, Rewards, and Recognition: A Nudge Guide," a groundbreaking analysis of ... field. Offering practical takeaways to apply immediately to IRR programs, the report highlights ...
(Date:4/27/2017)... Neb. (PRWEB) , ... April 27, 2017 , ... ... was named the 2017 North American CAREGiverSM of the Year for her extraordinary ... selects one of its 60,000 North American professional caregivers for the prestigious award ...
(Date:4/27/2017)... GA (PRWEB) , ... April 27, 2017 , ... Are ... a tragic spike in water-related accidents and drownings during the summer. While most of ... is that these situations occur every day. Very few people are taking the time ...
Breaking Medicine News(10 mins):
(Date:4/20/2017)... , April 20, 2017 Research and ... Market Size, Market Share, Application Analysis, Regional Outlook, Growth Trends, ... report to their offering. ... The global pharmacogenomics market was valued at US$ 7,167.6 Mn ... by 2024, expanding at a CAGR of 5.6% from 2016 ...
(Date:4/20/2017)... LUND, Sweden , April 20, 2017 /PRNewswire/ ... OTCQX: NEVPF) ("NeuroVive") today announced positive preclinical ... company,s preclinical compound for non-alcoholic steatohepatitis (NASH), ... NV556 has previously ... STAM™ NASH model. Today, NeuroVive,s scientists present ...
(Date:4/19/2017)... April 19, 2017 /PRNewswire/ - CRH Medical Corporation (TSX: CRH) (NYSE MKT: CRHM) ... & Co. Healthcare Investor Conference 2017 at the Sheraton Hotel in ... , Chief Executive Officer of the Company is scheduled to present ... Richard Bear and the Chairman of the Board, Tony ... ...
Breaking Medicine Technology: