THURSDAY, Aug. 9, 2001 (HealthDayNews) -- Researchers have found genetic mutations that cause a rare, inherited kind of high blood pressure, and they say the discovery may offer clues to the cause and treatment of the most common form of the condition.
Mutations in two genes that help govern the way the kidneys handle salty blood components are the cause of an unusual (and almost unspellable) genetic condition, pseudohypoaldosteronism Type II (PHAII), reports a team led by Dr. Richard P. Lifton of Yale University in the Aug. 10 issue of Science. While PHAII affects only a handful of families, variations in the genes "may underlie blood pressure variation in the general population," the researchers say.
"These findings have identified a new signaling pathway in the regulation of blood pressure that was previously unknown," says Lifton, chairman of Yale's department of genetics. "Consequently, these finding will spur further investigation of that pathway for a potential role in other forms of hypertension."
The road toward identification of one mutation began with a genetic analysis of 10 members of a family who had PHAII, one of whose symptom is high blood pressure. A sophisticated comparison of the genetic material of family members who did not have the condition showed that part of chromosome 12, one of the 23 gene-holding units found in human cells, was missing.
The researchers then used the database of the complete human genome -- a map that became available only in the last year -- and found that the deleted material is a gene designated WNK1, which makes an enzyme involved in the way the kidney controls blood levels of salt and other molecules that can affect blood pressure.
The next step was to do the same genetic work for a another family with chromosome 12- related PHAII. A slightly different deletion in the same area of the chromosome, also affecting WNK1, was detected. The deletion increases the activity of that enzyme five-fold, the researchers found.
Because earlier studies have linked some cases of PHAII to a different chromosome, number 17, the researchers then began looking for a WNK1-like gene on that chromosome. They found one, designated WNK4, in a region of the chromosome identified by earlier studies. They also found a number of different but related mutations of WNK4 in members of four families with PHAII. Those mutations probably act in the same way as the deletion on chromosome 12, increasing the activity of the enzyme, the researchers say.
The Yale finding joins a small group of discoveries that have linked relatively rare conditions causing high blood pressure to specific genetic flaws, says Tadashi Inagami, professor of biochemistry and former head of the hypertension research center at Vanderbilt University. But "that doesn't mean that that kind of mutation is a major cause of hypertension," he says. "There are certain mutations, but they contribute to only 5 to 10 percent of cases of hypertension."
The common kind of hypertension, or high blood pressure, that affects perhaps one in every four Americans is called "essential," meaning that its cause is unknown. Inagami says a number of contributing factors are known, including excess intake of salt, obesity and stress, but no one genetic factor has been connected to most cases of essential hypertension.
Lifton says one intriguing fact about the WNK4 gene is that "it lies smack in the middle of a chromosome segment that has previously been linked to hypertension in the general population. The new finding raises the possibility that WNK4 might be a gene affecting blood pressure in the general population."
That possibility will be explored in a research collaboration with the Framingham Heart Study, which has followed residents of a Massachusetts town for decades, Lifton says. Meanwhile, the Yale team will be studying "all the components of this signaling pathway," he says.
What To Do
While basic research goes on, it's wise to regularly check blood pressure, to treat high blood pressure when it's detected, and to avoid heavy salt intake, overweight and other risks for high blood pressure.
For basic information about high blood pressure, its detection and treatment, go to the American Heart Association or the National Heart, Lung and Blood Institute.
