Scientists uncover gene behind kidney disease risk
An international team of scientists has identified a mutation associated with a major indicator of chronic kidney disease, namely high levels of albumin protein in the urine. The discovery could lead to new ways of treating kidney disease and slowing its progression. The study, which was partly funded by the EU, is published in the Journal of the American Society of Nephrology (JASN). Chronic kidney disease is a serious problem worldwide; in Europe, around 1 in 10 are thought to be affected. Known risk factors for chronic kidney disease include diabetes and high blood pressure. However, elucidating the genetic factors underlying chronic kidney disease has proven difficult. In this study, the team reveals that a single mutation in a gene called CUBN is associated with a condition called albuminuria, in which the protein albumin leaks into the urine. Higher levels of albumin in the urine are a key indicator of chronic kidney disease and are associated with a greater risk of developing end-stage renal disease, which can only be treated by dialysis or a kidney transplant. In addition, albuminuria is associated with cardiovascular disease and mortality. The researchers uncovered the mutation by scanning and comparing the genomes of 63,000 people of European ancestry and 7,000 African Americans. The samples included both people with diabetes and people without it. The association between the CUBN mutation and albuminuria was found in people of European and African ancestry and in people with and without diabetes. 'The significance of this finding is that even though the field has known about cubilin (the protein encoded by CUBN) function from experimental animal studies, our study was the first to establish the link between a genetic variation in this gene and albuminuria,' commented one of the senior authors of the paper, Dr Linda Kao of Johns Hopkins Bloomberg School of Public Health in the US. 'The identification of CUBN and its association with albuminuria will lead to a multitude of follow-up work that will help us to begin to understand the mechanism behind albuminuria and, hopefully, will ultimately lead to novel treatment targets.' EU support for the work came from several projects. EURODIA ('Functional genomics of pancreatic beta cells and of tissues involved in control of the endocrine pancreas for prevention and treatment of type 2 diabetes'), ANEUPLOIDY ('Understanding the importance of gene dosage imbalance in human health using genetics, functional genomics and systems biology'), EUROSPAN ('European special populations research network: quantifying and harnessing genetic variation for gene discovery') and GENECURE ('Applied genomic strategies for treatment and prevention of cardiovascular death in uraemia and end stage renal disease') were all supported under the 'Life sciences, genomics and biotechnology for health' Thematic area of the Sixth Framework Programme (FP6). EPIC ('European prospective investigation into cancer, chronic diseases, nutrition and lifestyle') was funded under the 'Policy support' budget line of FP6. HYPERGENES ('European network for genetic-epidemiological studies: building a method to dissect complex genetic traits, using essential hypertension as a disease model') and EUNEFRON ('European network for the study of orphan nephropathies') were both funded under the Health Theme of the Seventh Framework Programme (FP7). The work also received EU support via a Marie Curie Intra-European Fellowship. Participating in the study were researchers from Austria, Belgium, Canada, Croatia, Germany, Iceland, Italy, the Netherlands, Norway, Sweden, Switzerland, the UK and the US.For more information, please visit: Johns Hopkins Bloomberg School of Public Health:http://www.jhsph.edu Journal of the American Society of Nephrology (JASN):http://www.jasn.org
Countries
Austria, Belgium, Canada, Switzerland, Germany, Croatia, Iceland, Italy, Netherlands, Norway, Sweden, United Kingdom, United States