How a common gene variant may contribute to higher blood pressure

A widespread genetic variant can change how artery walls contract and relax, shedding light on one inherited factor that can affect blood pressure. Researchers linked the effect to a protein that helps control gene activity in the muscle cells of blood vessels.

The finding may help pave the way for more precise hypertension treatments. It also underscores how a small DNA change can influence a biological pathway without determining a person’s health on its own.

In a study led by Michigan Medicine and published in The Journal of Clinical Investigation, scientists combined human genetic data with experiments in cells and mice. Their work centered on a regulatory protein known as JMJD3.

The muscle layer surrounding an artery helps determine how wide the vessel can open. When that muscle tightens, blood meets more resistance; when it relaxes, the channel widens.

JMJD3 helps regulate which genes are switched on in these muscle cells. Instead of acting like a simple blood-pressure switch, it affects a system that shapes how strongly vessels respond to chemical signals.

The researchers examined a DNA variant identified in earlier large-scale genetic studies. The more common form was tied to lower JMJD3 production and a modest rise in systolic blood pressure, the upper number in a reading.

Another line of research looks at a protein that links high blood pressure and diabetes.

In the genetic analysis, each copy of the common version was associated with an increase of about 0.47 millimetres of mercury. That represents a small average effect, not proof that carrying the variant inevitably leads to hypertension.

The team then studied the endothelin system, which helps regulate blood-vessel tone. Two receptors in this system help balance vessel tightening and relaxation.

When JMJD3 was reduced in experimental smooth muscle cells, that balance was disrupted. In mice, loss of the protein increased vessel constriction and blood pressure, and it also contributed to changes in the artery walls.

The researchers also tested a compound called BQ-123, which blocks the endothelin receptor involved in vessel tightening. It reversed hypertension in the affected mice, strengthening the case that this pathway mattered.

That treatment experiment helps connect the genetic discovery to a possible drug target. It does not mean that everyone who carries the common variant would respond to the same medicine.

Human blood pressure is influenced by many genes, along with diet, physical activity, kidney function, age and other factors. A pathway identified in controlled experiments still needs clinical testing before it can be used to guide treatment decisions.

The study goes beyond a statistical association by showing how a genetic difference can alter the behavior of artery cells. In the long run, that kind of insight could help researchers match therapies more closely to the biological causes of hypertension.

If you are interested in this topic, please read articles about The DASH diet is a simple way to lower high blood pressure, and Garlic could help lower high blood pressure, protect artery health.

For more information, please see articles about What should know about high blood pressure drugs and their side effects, and Potassium may be key to lowering blood pressure, study finds.

Source: Michigan Medicine.