Study on link between SNP and concentrations of serum creatinine

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.