Blood pressure genes found in the human kidney

Scientists have discovered 179 kidney genes that are responsible for high blood pressure – about 80% of which have never been associated with hypertension before, it was announced last night.

The findings by the international team, led by The University of Manchester, UK, and published in Nature Genetics, provide a new understanding of the genetic predisposition to hypertension and it is hoped some of these genes can be targeted by existing medicines.

The study examined datasets of human DNA and RNA from one of the world’s largest repositories of human kidney tissue-based omics and included analyses conducted at various molecular levels of kidney tissue combining together DNA, RNA and other layers from the same set of kidney tissue samples.

They also used Mendelian randomisation to screen for evidence of causal associations between thousands of variables and millions of genetic variants.

Team leader Maciej Tomaszewski, professor of cardiovascular medicine at the University of Manchester and a consultant physician, characterised how information inherited in DNA translates into genetic predisposition to high blood through changes in activity of certain kidney genes.

Senior author Professor Fadi J Charchar, from Federation University, Victoria, Australia, said: “Our studies filled an important gap in our knowledge through uncovering new genetic variants, kidney genes, molecular mechanisms and biological pathways of key relevance to genetic regulation of blood pressure and inherited susceptibility to hypertension.”

Professor James Leiper, associate medical director at the British Heart Foundation, which supported the research, 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.”

Professor Jeremy Hughes from Kidney Research UK, which also supported the research, added: “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.”

Uncovering genetic mechanisms of hypertension through multi-omic analysis of the kidney. Nature Genetics 6 May 2021.

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