Study points to gene's role in hypertension.

Genetic testing has provided the first direct evidence for a long-suspected inheritable predisposition toward hypertension, which afflicts more than 50 million Americans and is a major factor in cardiovascuiar disease, kidney failure, and stroke.

Although the specific cause of hypertension remains unknown in most cases, scientists believe the onset of the disease involves heredity, diet, exercise habits, and stress. The new finding is an important step toward understanding the genetic basis of the disease, says Jean-Marc Lalouel of the Howard Hughes Medical Institute at the University of Utah in Salt Lake City.

"This certainly opens the way ultimately toward identifying people that carry specific risk factors," comments Lalouel, who led the U.S. portion of the study. A French research team conducted a parallel, concurrent study. The two groups pooled their data and reported their results jointly in the Oct. 2 CELL.

In the long run, a genetic test for susceptibility to hypertension would enable physicians to shift emphasis to preventive therapies, perhaps blocking the irreversible onset of the disease later in life. Further genetic studies, says Lalouel, might also lead to better drug treatments for patients already affected.

The U.S. and French researchers targeted a gene that codes for a protein called angiotensinogen (AGT), an important raw material in the chemical process that regulates blood pressure. They examined DNA samples from a total of 379 pairs of hypertensive siblings from 215 families in Paris and Salt Lake City, as well as samples from 237 unrelated people who did not have high blood pressure. All study participants were white.

Although children inherit one of two versions of the AGT gene from each parent, the hypertensive siblings in the study shared the same parental AGT gene significantly more often than they would have by chance, the investigators found. This suggests that a tendency toward hypertension can pass from parent to child.

The researchers also identified a number of variations in the AGT gene, two of which appeared more often in hypertensives than in people with normal blood pressure. Lalouel and his colleagues believe these variants may indicate the predisposition toward high blood pressure.

In an effort to establish a more direct link between the gene variants and the disease, the researchers determined that hypertensives who inherited one particular version of the gene had elevated blood levels of AGT. Previous studies had linked excess AGT in the bloodstream to high blood pressure.

The study suggests, but does not prove, that people who develop hypertension may have inherited a tendency to do so, Lalouel explains. He warns that the data gathered so far do not demonstrate a cause-and-effect link between high blood pressure and a specific gene or genes.

Victor J. Dzau of the Stanford University School of Medicine reiterates this point. "The study itself is exciting, the results are compelling, but it certainly does not prove that we found the gene, or [one of many genes], for hypertension," he says.

Dzau, who has investigated the genetics of high blood pressure in rats, says the new work demonstrates that researchers can use the tools of modern genetics in humans to study complex, multigene diseases such as hypertension. Blood pressure regulation in humans, he points out, may involve anywhere from 20 to 50 genes.

Lalouel and his colleagues plan to extend their research to the study of hypertension in blacks, who develop the disease more frequently than whites (SN: 10/19/91, p.254). The researchers will also attempt to clarify sex-based differences in inheritance patterns that emerged during the study. Such differences, says Lalouel, may trace to estrogen's ability to switch on the AGT gene.