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.

High blood pressure and diabetes are known risk factors for CKD, but evidence from multiple studies indicates that there is a genetic component to the condition too.  Rare mutations that cause kidney disease have been identified, but finding common variations that impact susceptibility to CKD has been difficult.  Now a new study, published online this week in the journal Nature Genetics, shows that a variation in the gene that encodes the most common protein found in urine is associated with kidney disease risk.

The Tamm-Horsfall protein, encoded by the UMOD gene, was discovered almost 60 years ago, but its role in the body continues to baffle scientists.  Some studies have suggested it may be involved in protection against inflammation and infection, while others have suggested it functions in kidney development.

Researchers found that each G at rs4293393 in the UMOD gene decreased the odds of CKD by 24%.  Approximately 18% of people with European ancestry have at least one G at this SNP.

(23andMe customers can check their data for rs4293393 using the Browse Raw Data feature This SNP is a proxy for the SNP found in the study, rs12917707.)

“We have known for a long time that a higher level of proteins, such as albumin, which aren’t usually present in urine, is a risk factor for kidney disease and its progression. The UMOD finding suggests that Tamm-Horsfall protein, which is thought to be a normal part of the urine, deserves attention since its genetic variation relates to risk,” said Josef Coresh, professor in the Johns Hopkins Bloomberg School of Public Health’s Department of Epidemiology and Biostatistics and a co-author of the study, in a statement.

Another study from Johns Hopkins, appearing last year in Nature Genetics, found an association between variations in the MYH9 gene and end-stage renal disease in African Americans.

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Chronically high blood pressure is a serious health problem that affects about one out of every three adults and contributes to approximately 17.5 million deaths worldwide each year.  While there are many things people can do to try to keep their blood pressure down – lower salt intake, maintain a healthy weight and drink in moderation – studies have shown that genetics also plays a part.

But finding common genetic variations that affect blood pressure hasn’t been easy. Just five months ago The Spittoon reported on the first validated association in Europeans. Now, two large consortia have identified several more.  Their findings, published online this week in the journal Nature Genetics, expand the current understanding of how blood pressure is determined and may point the way towards targets for new drugs for treating possibly preventing hypertension.

“None of the genes we identified as having common variation are part of the system we know about that regulates blood pressure – the genes identified are not the ones targeted by current prescription drugs to control hypertension.  If we can increase the number of genes implicated in blood pressure maintenance…our understanding of the biology will change completely,” said Aravinda Chakravarti, head of the Center for Complex Disease Genomics in the McKusick-Nathans Institute of Genetic Medicine at Johns Hopkins University School of Medicine and a co-author of one of the studies, in a statement.

The two research groups analyzed data from an enormous number of people – more than 50,000 in the Global BPgen study and more than 29,000 in the CHARGE study.  Such large samples are needed because variation in blood pressure is likely due to many variations, each with very small effects.

After conducting their own analyses, the researchers from each consortium shared their findings with each other, allowing the scientists to further confirm their results.  All together, six distinct variations associated with systolic blood pressure (SBP) and nine associated with diastolic blood pressure (DBP) were found and confirmed between the two studies. The Global BPgen consortium also studied more than 12,000 South Asian Indians and found evidence for association between blood pressure and two of the SNPs identified in the European studies.

(23andMe customers can check their data for many of these SNPs using the Browse Raw Data feature.  See tables at the end of this post for more information.)

Further analysis of the Global BPgen results showed that all of the SNPs associated with SBP through the genomewide analysis were similarly related to DBP, and vice versa. And not surprisingly, all of the SNPs the researchers identified were also associated with hypertension; the version of each SNP linked to lower blood pressure was also decreased a person’s odds of having the condition.

The effects of the individual SNPs were small, but the authors of both studies point out that small changes in blood pressure can translate to important changes in the risk of heart disease and stroke.  For example, the authors of Global BPgen study say that lowering SBP by 2 mmHg has been estimated to translate into 6% lower risk of stroke and 5% lower risk of coronary heart disease.  The authors of the CHARGE study cite other data showing that a prolonged increase in DBP of 5 mm Hg is associated with a 34% increase in risk for stroke and a 21% increase in the risk of coronary events.

All SNPs that were found to have significant association with blood pressure by both groups after they shared their data with each other are given below. Those SNPs for which 23andMe can provide data are linked to the Browse Raw Data feature.  Some linked SNPs are proxies for the SNPs described in the original articles and are noted as such.  The information in the first table applies only to people with European ancestry.  The second table provides information on the findings of the Global BPgen study of South Asian Indians.

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The ease with which you can measure your blood pressure using one of those cuff machines at the pharmacy belies just how important this number is to your health.  Chronically high blood pressure, which affects about one in three adults in the United States, increases the risk for stroke, heart attack, heart and kidney failure and aneurysms.

Studies have so far failed to find common genetic variations associated with blood pressure, although there is strong evidence that genetic factors do play a part.  Now, new research published online Sunday in Nature Genetics has identified two variants that not only help explain differences in blood pressure, but could also point the way to new therapeutics.

In a study of 14,473 people, Christopher Newton-Cheh and colleagues identified three genetic variations associated with increased blood levels of two different “natriuretic peptides” – blood pressure-lowering hormones released by heart cells.

Further investigation of these three variations in an additional 29,717 people revealed that two of them are also associated with small reductions in blood pressure – 0.9-1.5 mm Hg for systolic (the top number in a blood pressure reading) and 0.3-0.8 mm Hg for diastolic blood pressure (the bottom number).  The variations were also linked to 10-15% decreased odds of having high blood pressure or being prescribed blood pressure-lowering medication.

(23andMe customers can use the table at the end of this post to check their data at these SNPs.)

While the reductions in blood pressure associated with these variations may seem small (a normal blood pressure reading is something like 120 mm Hg/80 mm Hg), the authors note that even a 1 mm Hg reduction in systolic blood pressure has been associated with an 8% lower risk of death from stroke or heart attack.  They speculate that lifelong lowered blood pressure, as might be expected in someone carrying these genetic variations, could magnify this effect.

According the authors, there is already active research aimed at finding drugs that activate natriuretic peptides.

“Our finding that genetic variation … associated with natriuretic peptide concentrations was also associated with blood pressure and hypertension suggests that these agents might prove useful for the treatment of hypertension,” the authors write, although they do add that more studies will be necessary to fully explore the role of the genetic variants in blood pressure regulation and cardiovascular physiology.

These results are currently applicable only to people with European ancestry.

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