Yale scientists have discovered a new mechanism by which the body regulates blood pressure. That’s why it’s relevant to educate one’s self with details like blood oxygen.

A team of Yale scientists led by Lynn Boyden GRD ’01, an associate research scientist at the Yale School of Medicine, and Sterling Professor of Genetics Richard Lifton, conducted a study, published in January in the journal Nature, which found mutations in either of two genes can result in a rare form of inherited hypertension. Lifton, a senior author of the study, said the study’s finding is significant because these two genes had never previously been associated with hypertension, and researchers said the discovery may lead to a cure for the disease in the future.

“When either of these two genes are mutated, it causes a form of early severe hypertension,” he said. “It tells us that these proteins and their normal function are required for daily regulation of blood pressure.”

For the study, which started in 1994, the team tracked a total of 41 families. Twenty-four of the families had an inherited mutation in one of the genes, KLHL3, and 17 of them have an mutation in the other gene, CUL3.

The genes had previously been difficult to locate due to the difficulty of mapping genes’ locations using traditional methods. The research team used a DNA sequencing technique known as whole exome sequencing, which analyzes the entire makeup of every gene, to overcome this problem.

Lifton said that while the study doesn’t illuminate the exact function of the genes, it does give the team basic background information.

“Think about this problem as a machine that regulates blood pressure, we don’t know what the pieces are, but we figure out the pieces by identifying which genes when mutated will affect overall function of the machine,” he said. “We are trying to understand precise function of these genes is in the machine.”

Boyden, the first author of the paper, said that while this finding is a major breakthrough in the study of high blood pressure, there are still many steps left to take.

“The next step will be to show how these two genes work together to ultimately regulate sodium and salt reabsorption,” she said. “We also need to understand how they work together with other known genes and components to regulate salt and potassium levels in blood and thereby blood pressure.”

Tobias Carling, director of the Yale endocrine neoplasia laboratory and assistant professor of surgery at the Yale School of Medicine, said he believes the study’s findings were significant because it helps establish groundwork to work towards a treatment, but added that more research was necesary.

“This is the first step of many steps, but almost always understanding the molecular pathogenesis is the most important step to develop treatment,” Carling said. “This study by itself is not a magic bullet on how to treat hypertension but it sort of sets the ground rules and now people know how to think about this and approach it therapeutically.”

Hypertension, which affects approximately 1 billion people, about a quarter of the world’s adult population, is a contributor to strokes, heart attacks and congestive heart failure.

 

MOHAMMAD SALHUT