Research reveals new kidney genes causing high blood pressure
An international research team supported by Kidney Research UK and the British Heart Foundation has discovered 179 kidney genes responsible for high blood pressure.
The new research, led by researchers at the University of Manchester and published today in Nature Genetics, has revealed how changes in kidney genes can cause high blood pressure. Over three quarters of the 179 new genes discovered by the team have never been linked to high blood pressure before.
As many of these genes are targets for drugs that already exist, this research has huge potential for developing targeted ways to treat high blood pressure.
High blood pressure can have serious consequences
We know that the kidneys play a very important role in regulating blood pressure. If left untreated, high blood pressure increases the risk of heart attacks, strokes and chronic kidney disease. High blood pressure can run in families, but we know very little about the genes involved.
Professor Maciej Tomaszewski from the University of Manchester, who led the research team said: “High blood pressure is a key driver of coronary heart disease and stroke and the single most important cause of disability and premature death worldwide.
Yet, our understanding of the role of genes in development of this condition has been incomplete.”
Linking DNA changes to high blood pressure
A genome-wide association study (GWAS) is a method used by researchers to analyse the genome – the entire DNA, or genetic code that a person has. The scientists studied the genomes of many people to find the changes in DNA code that tend to be linked to specific diseases or characteristics.
Scientists have previously carried out GWAS studies to find DNA changes that are linked to high blood pressure. Although this information is very useful, to find effective treatments we need to understand exactly how these changes in DNA lead to an increase in blood pressure. This research has bridged a knowledge gap between our understanding of DNA changes that are passed through families and how the kidney regulates blood pressure.
How do changes in DNA cause an increase in blood pressure?
Even though almost all the cells in our body contain the same DNA sequence, each type of cell has a different set of genes that, when they are switched on, make the functional products such as proteins that are needed for the cell to work correctly.
Because the kidneys have a key role in regulating blood pressure, researchers wanted to understand if the changes in DNA that have been linked to high blood pressure in the GWAS studies were affecting which kidney genes are switched on.
Studying human kidney cells
The research team analysed information from 430 samples taken from human kidneys. They studied the DNA code, which genes were switched on in the kidney cells as well as epigenetic changes in the cells — changes that affect how the body reads a section of DNA code without changing the code itself.
Using all this information, the team showed how changes in the DNA code influence kidney genes, revealing new kidney genes and pathways that control blood pressure and uncovering potential targets for treatment.
Offering hope to kidney patients
Professor Jeremy Hughes, kidney doctor and chair of trustees at Kidney Research UK said: "High blood pressure is both a cause and consequence of kidney disease and we need better treatments to protect patients from harm such as strokes and heart attacks.
He continues: “This innovative study harnesses the power of a kidney tissue biobank and state-of-the-art genetic analysis to identify novel genes that link the kidney to high blood pressure. We hope this new knowledge will eventually lead to new treatments that benefit kidney patients."
Professor James Leiper, Associate Medical Director at the British Heart Foundation said: “We have known for many years that the kidney is a major regulator of blood pressure, but our understanding of precisely how the kidney controls blood pressure is incomplete.
“The identification of this large set of genes that appear to directly affect blood pressure fills in an important missing piece of that puzzle. The researchers have also found a subset of these genes that are a potential new target for the treatment of hypertension.
“This is important because many people taking existing medications still struggle to control their blood pressure. If doctors have more tools to work with then it will help stop thousands of lives being lost each year from this potentially preventable condition.”
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