Genetic Factors Can Help Predict Risk for Kidney Disease

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Israeli and American researchers have identified new genetic data that could be used in the future to predict who will develop end-stage kidney disease (ESKD). ESKD requires dialysis or transplantation to sustain life, and is fatal in most regions of the world, where these treatments are not available.

Published in the February 9th issue of Human Molecular Genetics, the results could someday benefit the estimated 40 million people in the U.S. alone who suffer from various degrees of chronic kidney disease, the prelude to ESKD.

Led by Prof. Karl Skorecki of the Technion-Israel Institute of Technology Faculty of Medicine, and Dr. Doron Behar of Rambam Medical Center, the researchers discovered highly informative DNA markers in the MYH9 gene. These markers are closely linked to a presumed variant of the cellular nano-motor protein that the gene encodes, and they help explain the high incidence of ESKD requiring dialysis or transplantation among Americans of African ancestry – including African and Hispanic Americans.

The findings were the result of analyzing markers in the MYH9 gene in a group of 1,425 African American and Hispanic American subjects, including dialysis patients and control healthy subjects. The gene was first reported to be associated with ESKD by two U.S. teams in 2008, and one of these teams led by Dr. Jeffrey Kopp and his colleagues of the National Institutes of Health are collaborators on the current Technion study.

These high risk markers are found in up to 60% of people originating from western and southern African regions, and their presence raises the risk of the disease by as much as three to four fold in individuals carrying risk markers at both parental copies of chromosome 22, on which the gene is located. The actual emergence of kidney failure requires a combination of the risk variant of the gene, together with another trigger.

“These findings can advance the use of genetic screening for those at high risk of developing kidney failure, which might enable preventative early treatment in at risk individuals,” said Skorecki. “The research findings will also advance future research into the mechanisms wherein abnormalities in the protein encoded by MYH9 affect the normal filtering function of the kidney, and thereby could lead to the development of new methods for treating and preventing terminal kidney failure.”

Genetic factors were once believed to play only a minor role in the development of certain rare types of kidney disease that run in families. However, careful analyses over the past decade have uncovered ethnic or population-based differences in the prevalence of common forms of kidney disease that were not thought to have a strong hereditary component, based on family pedigree analysis. Socio-economic factors were not able to explain these ethnic disparities in kidney disease, leading several U.S. teams – as well as the Technion-led team – to search for genetic factors. Previous findings by the Technion team showed that Ethiopians are protected from some forms of kidney disease to which people from other parts of Africa are more susceptible. The Technion team postulated that population-based differences in genetic factors within Africa might provide the explanation, and are currently testing the MYH9 kidney failure markers in Ethiopians residing in Addis Ababa and in Haifa, Israel.

Also contributing to this research were Technion-Israel Institute of Technology doctoral students Shay Tzur and Sivan Bercovici, and researchers from Rambam Medical Center, Tel Aviv University, the Hadassah Medical Center in Jerusalem, and the National Institutes of Health and the National Cancer Institute in the U.S.

The Technion-Israel Institute of Technology is Israel’s leading science and technology university. Home to the country’s first winners of the Nobel Prize in science, it commands a worldwide reputation for its pioneering work in nanotechnology, computer science, biotechnology, water-resource management, materials engineering, aerospace and medicine. The majority of the founders and managers of Israel’s high-tech companies are alumni. Based in New York City, the American Technion Society (ATS) is the leading American organization supporting higher education in Israel, with offices around the country.

Source:  American Technion Society

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