Chronic kidney disease (CKD), characterized by the gradual loss of the kidneys’ filtering ability, currently affects about 10-13% of adults in the United States. Patients suffering from the most severe form of the condition, end-stage renal disease, require dialysis or a kidney transplant to survive.
Rare mutations that cause kidney disease have been identified, but finding common variations that impact susceptibility to CKD has been difficult. Research published in 2009 showed that a variation in the gene that encodes the most common protein in urine could increase risk for CKD. Now new research, published recently in the journal PLoS Genetics, replicates this finding and shows that the variant may act by influencing how the kidneys adapt to age-related risk factors for kidney disease.
The new results, obtained by analyzing DNA from several thousand Icelandic and Dutch individuals, upheld the previous finding that each copy of the more common A version of rs4293393 in the UMOD gene, which encodes the Tamm-Horsfall protein, is associated with about 25% higher odds of CKD.
(We previously reported this in The Spittoon as each copy of the less common G version being associated with about 20% lower odds of CKD. These numbers are consistent. It’s really just two different ways of looking at the same thing. We’ve switched to talking about the more common A version here because this is how the researchers frame it in the most recent study. 23andMe customers can check their data for rs4293393 using the Browse Raw Data feature. This SNP is equivalent to rs13333226 reported in the Kidney Disease Preliminary Research Report.)
To further assess the effects of rs4293393, the researchers turned their attention to measurements of serum creatinine concentration (SCr), an indicator of kidney function. Higher SCr is associated with decreased filtering ability in the kidney. They found that in the Icelandic sample, the A version of the SNP affects SCr levels in an age-dependent manner. Before age 50, this variant doesn’t have much of an affect. But thereafter each copy of a A is associated with higher SCr every year, especially around age 70. The effect of rs4293393 was intensified in people with hypertension compared to those without a diagnosis of high blood pressure, as well as in those with type 2 diabetes compared to those without.
Based on their results, the researchers speculate that rs4293393 affects the vulnerability of the kidney to damage as a person ages.
“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 [rs4293393] is now a validated risk factor for kidney disease, but we have also shown it can be even more meaningful if looked at in the context of age and broader health history,” said the study’s senior author, Kari Stefansson, in a press release.
SNPwatch gives you the latest news about research linking various traits and conditions to individual genetic variations. These studies are exciting because they offer a glimpse into how genetics may affect our bodies and health; but in most cases, more work is needed before this research can provide information of value to individuals. For that reason it is important to remember that like all information we provide, the studies we describe in SNPwatch are for research and educational purposes only. SNPwatch is not intended to be a substitute for professional medical advice; you should always seek the advice of your physician or other appropriate healthcare professional with any questions you may have regarding diagnosis, cure, treatment or prevention of any disease or other medical condition.