Kidney gene discovery unlocks door to high blood pressure answers

An international team of scientists has discovered kidney genes responsible for high blood pressure, paving the way for new opportunities to treat the disease.

The discoveries, published in Nature Genetics, one of the world's leading journals, shed new light on researchers' understanding of genetic predisposition to high blood pressure. The researchers identified 179 kidney genes responsible for high blood pressure.

Federation University Director of Health Innovation and Transformation Centre (HITC) Fadi Charchar, a senior author on the study, said researchers had unprecedented access to vast datasets of human DNA and RNA.

"We have known for many years that some part of the DNA contributed to high blood pressure or blood pressure regulation, but we never knew the exact molecules because there weren't many available human kidney samples to look at. We now have this fantastic kidney resource to interrogate," Professor Charchar said.

"In the last 20 years, there's been an explosion in DNA studies, and, for this study, we have dug down to the next level, which is RNA."

RNA are the messages that genes produce to tell cells how to function and how to make proteins. It can be determined which genes are active in a cell by the RNA produced by the cell's DNA.

The study was led in the UK at the University of Manchester and funded by the British Heart Foundation, Kidney Research UK. In Australia, it was led by Federation University and funded by the National Health and Medical Research Council. Researchers were given access to datasets of human DNA and RNA from possibly the world's largest repository of human kidney tissue.

High blood pressure is the leading risk factor for heart disease in Australia, with an estimated 1.2 million people aged 18 years and over having one or more conditions related to heart or vascular disease, including stroke, in 2017–18, according to the Australian Bureau of Statistics.

It is known to run in families, but the exact mechanisms through which genes influence individuals' predisposition to hypertension is not clear.

The study is the culmination of a five-year effort for the researchers and continues a collaboration with the University of Manchester that extends to two decades.

The team led by Professor Maciej Tomaszewski at the University of Manchester and Professor Charchar at Federation University characterised how information inherited in DNA translated into genetic predisposition to high blood through changes in activity of certain kidney genes.

Priscilla Prestes, a Research Fellow in the School of Science, Psychology and Sport, travelled to Manchester to study the samples used in the research and has recently been awarded a Victoria Fellowship to go back to the UK to complete further study on the samples.

RNA recently used to make the Pfizer COVID vaccine is much more easily degraded than DNA, adding significant complexity to the study and the need for onsite processing in the UK.

"This study gave us an idea in high-fidelity how new molecules were helping to regulate blood pressure through the kidney," Professor Charchar said.

He said the findings could lead to new treatment opportunities.

"Our studies filled an important gap and propel drug discovery for the number one risk factor for death in the world."

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