A SNP on chromosome 16 appears to confer risk by affecting how the renal system adapts to the impact of aging and the onset of other common diseases
Reykjavik, ICELAND, 29 July 2010 – Scientists at deCODE genetics and colleagues at Radboud University in the Netherlands today describe how the impact of a single letter variation in the sequence of the human genome (SNP) conferring risk of kidney disease varies with age and with the onset of other diseases. The study provides independent confirmation of the association made in an earlier study between a version of the the SNP, located on chromosome 16p12, and risk of chronic kidney disease (CKD). It also confirmed the link between the SNP and concentrations of serum creatinine (SCr), a key indicator of kidney function. But the deCODE team then used its detailed population-based data in Iceland to go further, demonstrating that the impact of the at-risk version SNP on risk of kidney disease and SCr increases with age and if carriers develop high blood pressure or type 2 diabetes. At the same time, the SNP was shown in a large Icelandic and Dutch case-control cohort to protect against the formation of kidney stones.
“The common diseases happen at the interface between genes and the environment, and this study offers a clear and medically useful example of this dynamic in action. This SNP is now a validated risk factor for kidney disease, but we have also shown how it can be made even more meaningful if looked at in the context of age and broader health history. It is directly adjacent to the gene econding uromodulin, or UMOD, the most abundant protein in human urine. It therefore appears that it confers risk by modulating how the kidneys adapt to age itself and to the accumulation of environmental insults, such as hypertension and diabetes, over time. We believe this mechanism may be a fruitful subject for further research aimed at preventing and treating kidney disease,” said Kari Stefansson, deCODE’s Executive Chairman and President of Research and senior author of the study.
The paper, “Association of variants at UMOD with chronic kidney disease and kidney stones – role of age and comorbid diseases,” is published online in the open-access journal PLOS Genetics, at www.plosgenetics.org.
Headquartered in Reykjavik, Iceland, deCODE genetics is a global leader in analyzing and understanding the human genome. Using its unique expertise and population resources, deCODE has discovered key genetic risk factors for dozens of common diseases ranging from cardiovascular disease to cancer. deCODE employs its capabilities to develop DNA-based tests and personal genome scans to better understand individual risk and empower prevention. It also licenses its tests, intellectual property and analytical tools to partners, and provides comprehensive genotyping, sequencing and data analysis services to companies and research institutions around the globe. Through its CLIA- and CAP-certified laboratory deCODE offers DNA-based tests for gauging risk and empowering prevention of common diseases, including deCODE T2™ for type 2 diabetes; deCODE AF™ for atrial fibrillation and stroke; deCODE MI™ for heart attack; deCODE ProstateCancer™ for prostate cancer; deCODE Glaucoma™ for a major type of glaucoma; and deCODE BreastCancer, for the common forms of breast cancer. Through its pioneering personal genome analysis service deCODEme™, deCODE enables individuals to better understand their risk of dozens of common diseases and to learn about their ancestry and other traits. Visit us on the web at www.decode.com