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Archive - May 10, 2009

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Most Common Protein in Urine Associated with Altered Kidney Disease Risk

An international research team has shown that a common genetic variant of the gene (UMOD) for the most common protein in normal human urine is associated with a lowered risk of chronic kidney disease. This protein is the Tamm-Horsfall protein and, although it has been known for almost 60 years, its functions are not well understood and its relationship to chronic kidney disease risk was not known previously. "Previous research showed that rare mutations in the UMOD gene cause hereditary forms of severe kidney disease. Our research indicates that a common genetic variant with a frequency of 18 percent in populations of European ancestry is associated with about 25 percent lower risk of chronic kidney disease," said the lead author of the study, Dr. Anna Köttgen, a researcher in the Johns Hopkins Bloomberg School of Public Health. In their genome-wide association studies, the researchers also identified two additional genes (SHROOM3 and STC1) that were associated with altered risk for reduced kidney function and chronic kidney disease. The study was published in the May 10 online edition of Nature Genetics. [Johns Hopkins release] [Nature Genetics abstract]

Blocking Single Target May Prevent Lethal Aneurysms

Researchers have shown that removal of a single key protein can prevent early damage in blood vessels from triggering a later-stage, frequently lethal complication of atherosclerosis. By eliminating the gene for a signaling protein called cyclophilin A (CypA) from a strain of mice, the team was able to provide complete protection against abdominal aortic aneurysm (AAA). AAA leads to 15,000 deaths a year, mostly in aging men, when aneurysms rupture to spill blood into the abdomen, a fatal event in 90 percent of cases. When study mice were engineered to remove their CypA gene, none from that group developed AAA in the face of the hypertension and high cholesterol known to accelerate it. In contrast, 78 percent of mice with "normal" amounts of CypA developed AAA under the same conditions, 35 percent with a fatal rupture. The researchers also found high CypA levels in the rupture-prone vessels of humans with AAA, and that major drugs like statins reduce CypA levels, which may partly explain their benefit. “It is extremely unusual for the removal of one protein to provide absolute protection, but it makes perfect sense because cyclophilin A promotes three of the most destructive forces in blood vessels: oxidative stress, inflammation, and matrix degradation," said Dr. Bradford C. Berk, of the Aab Cardiovascular Research Institute at the University of Rochester Medical Center, and senior author of the study. "We are working to design anti-CypA drugs that will diminish the disease processes underlying AAA, atherosclerosis and hypertension." This study was published in the May 10 online edition of Nature Medicine. [Press release] [Nature Medicine abstract]