Genetic Mutation That Causes Common Type of High Blood Pressure Identified

Researchers at Queen Mary University of London and Barts Hospital have found the genetic cause of a common form of high blood pressure and shown how it can be cured. Their research is now published in Nature Genetics.

Flummoxed by fluctuations

One in twenty people have a form of hypertension caused by a tiny, non-cancerous tumor called an adenoma that develops in the adrenal glands that sit atop our kidneys. The adenomas increase the level of a hormone called aldosterone, which controls how much salt is in the body, leading to raised blood pressure. The researchers have now mapped the mutation that leads to the formation of these adenomas.

The mutation’s effect on the body is complex and partially explains why diagnosis of hypertension has proved so challenging in some patients. The variant alters a protein called CADM1. It interrupts cellular communication, meaning that signals that would normally halt aldosterone production are silenced. Aldosterone levels naturally fluctuate throughout the day, meaning that traditional diagnostic techniques can produce a negative result if patients are measured at the wrong time of day.

A more positive finding was that, in most cases, the adenoma is isolated to just one adrenal gland and removal of the affected gland stopped the hypertension, even in cases that have proved stubbornly resistant to pharmacological treatment for years.

Routine practice

The next step is to make sure people with this form of hypertension are diagnosed in routine clinical practice. Aldosterone mutations are not commonly looked for after high blood pressure is identified. The researchers recommend that aldosterone levels should be measured via repeated measurement of the hormone’s levels in urine rather than a single analysis. One patient that kickstarted the study was only identified as having an adenoma because of participation in a related clinical trial for difficult-to-treat hypertension.

Professor Morris Brown, co-senior author of the study and professor of endocrine hypertension at Queen Mary University of London, said: “In the 900^th anniversary of Barts Hospital, this story illustrates benefits from the virtuous circle of science and medicine. Most patients consent to our undertaking non-routine molecular analyses of their surgical samples, from which we discover how their hypertension was caused, and how to cure it in future patients. Because the aldosterone nodules in this study were so small, we are now investigating whether momentary cauterization of the nodule is an alternative to surgical removal of the whole adrenal gland.” 

Reference: Wu X, Azizan EAB, Goodchild E, et al. Somatic mutations of CADM1 in aldosterone-producing adenomas and gap junction-dependent regulation of aldosterone production. Nat Genet. Published online June:1-13. doi:10.1038/s41588-023-01403-0

This article is a rework of a press release issued by Queen Mary University of London. Material has been edited for length and content.