Scientists identify kidney genes that ‘appear to directly affect blood pressure’

High blood pressure runs in families but the mechanisms through which genes influence a person’s predisposition to hypertension have not been clear.
High blood pressure runs in families but the mechanisms through which genes influence a person’s predisposition to hypertension have not been clear.

Researchers have discovered 179 kidney genes that may be responsible for high blood pressure, potentially leading to new strategies for treating the condition.

Known as the silent killer, high blood pressure is one of the most common diseases and remains the key risk factor for strokes and heart attacks.

The condition – also known as hypertension – runs in families, but the exact mechanisms through which genes influence a person’s predisposition to hypertension is not clear.

The findings published in Nature Genetics shed new light on the understanding of this.

Researchers, led by Professor Maciej Tomaszewski at the University of Manchester, characterised how information inherited in DNA translates into genetic predisposition to high blood pressure through changes in activity of certain kidney genes.

The studies included comprehensive analyses conducted at various molecular levels of kidney tissue combining DNA, RNA and other layers from the same set of kidney tissue samples.

They also used a statistical method – called Mendelian randomisation – to screen for evidence of causal associations between thousands of variables and millions of genetic variants using the high-performance computing resources hosted at the university.

According to the study, around 80% of 179 genes discovered by the team have never before been associated with high blood pressure.

They say some of these genes can be targeted by existing medicines, creating new opportunities to treat the condition.

Principal investigator Prof Tomaszewski, professor of cardiovascular medicine and and a consultant physician, said: “Hypertension 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.”

Professor Andrew Morris, from the University of Manchester, said: “Through our unparalleled access to the kidney tissue resource, we provide evidence for the role of the kidney as the mediator of common genetic effects on blood pressure and a potentially causal role of blood pressure in the development of renal disease.”

First author, Dr James Eales from the University of Manchester, said: “By explaining the molecular mechanisms of hypertension embedded in the kidney, our study will ultimately lead to advancements in patient-centred diagnostic accuracy in hypertension.

“It will also lead to new targeted strategies to lowering blood pressure, thereby accelerating progress in precision medicine.”

While Professor Tomasz Guzik, from the University of Glasgow, said: “These exciting discoveries uncover a range of new possible mechanisms of hypertension, some related to blood vessels, kidneys, but also body immune defences, and pave the way for the development of novel genetic therapies for blood pressure.”

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.”