Gene Search Builds Knowledge about High Blood Pressure

A multidisciplinary research project looking at the genetics of hypertension, including a major study of the condition in Milwaukee's African-American population, hasn't yet revealed specific genes that predispose people to high blood pressure. However, several areas of the genome have been identified that are linked to hypertension.

The researchers have designed similar studies involving African-Americans in Milwaukee and a Caucasian French-Canadian population. One phase of the research (published in the May 2005 American Journal of Human Genetics) was a study of 120 French-Canadian families in an isolated region of Quebec, Canada. Researchers looked for genetic markers for hypertension in a scan of the total genome of study participants and found 46 chromosomal regions associated with hypertension. The researchers described this as a big step down the road to a simple blood test to diagnose specific genetic causes of high blood pressure.

Findings from the study of African-Americans in Milwaukee will be used to confirm and extend results from the French-Canadian group, said Theodore Kotchen, MD, Medical College of Wisconsin Professor of Medicine and Associate Dean of Clinical Research.

"The work is ongoing and the search for genes continues," said Dr. Kotchen. "I wish I could report that we have found genes, which we have not, but we do have some interesting leads. We've seen roughly 3,500 people in Milwaukee, all African-American. About half of them have hypertension and about half don't. We've been able to characterize some of the physiological correlates of hypertension in this population as well as in the related study of the Caucasian French-Canadian population."

A Very Complex Disease
The Medical College Department of Medicine is conducting the Milwaukee study under the direction of Dr. Kotchen and Allen W. Cowley, Jr., PhD, Chairman and Professor of Physiology. Other principals are Professor of Medicine Clarence E. Grim, MD, and Professor and Director of the Health Policy Institute Division of Epidemiology Jane M. Kotchen, MD (quotes in this article are from Dr. Theodore Kotchen). Heading up the research on the Canadian side is Dr. Pavel Hamet, MD, director of research at Centre Hospitalier de L'Universite de Montreal.

Additional information about "high blood pressure genes" in humans comes from Dr. Cowley's work with rats. Rats are appropriate subjects for such research, as they contain about 95% of the same genes as humans.

Advanced testing and analysis techniques are being applied to the data from all three populations - rat, Caucasian French-Canadian and African-American Milwaukeean - to further zero in on the regions that contain blood pressure influencing genes, and ultimately to specific genes that play the key roles in the development of hypertension.

Benefits in the Short Term
The study of the African-American population in Milwaukee will likely yield important results well before the elusive genes are identified, said Dr. Kotchen. "I think we will know more about the physiologic causes of hypertension in African-Americans," he said. "And we will use that information to develop the most effective strategies to prevent and treat hypertension in African-Americans.

"The practical implications of the genetic data are probably a little farther off than that, because Mother Nature guards her secrets carefully. Once we've identified genetic contributions to hypertension, we should be able to identify those individuals who are at risk for developing hypertension and introduce preventive strategies at a much younger age.

"We may also then be able to identify individuals who are more apt to respond to different classes of anti-hypertensive drugs." The "simple blood test" to help predict, diagnose and treat hypertension is probably a long way off, said Dr. Kotchen, who described that aspect of the work "a long-term endeavor."

"We're looking at the relationship of blood pressure to other risk factors for cardiovascular disease, such as blood cholesterol, obesity, abdominal obesity, and exercise," said Dr. Kotchen. "I think that within the next year or two, or sooner, we will be able to make some important statements about what we think are the most important correlates of blood pressure, and that would suggest preventive strategies or treatment strategies."

New Study Participants Welcome
Study participants are still being recruited in Milwaukee. Interested African-American females or males between the ages of 18 and 55 can call 800-366-1949 toll-free for more information.

"We're hoping to study in the range of 800 people as inpatients, roughly 400 people with hypertension and 400 normal test people," said Dr. Kotchen. "To date we've studied about 500 total. One important determinant of how much longer we will continue the study is funding. This is an NIH-funded project-my guess is the project will be funded for at least another two or three years.

"If you were a participant in the study, you would initially be seen as an outpatient during a clinic visit. The clinic visit is quite simple. We ask you a few questions about your medical history, your family history, particularly as it relates to hypertension. We measure your blood pressure, your height and weight. We get a blood test to screen for cholesterol and for kidney disease.

"Then, if you qualify according to certain blood pressure, age and other criteria, and you're interested in participating further, you would be invited to come into the hospital for two days. There we do considerably more extensive testing of renal function, cardiac function, measure a number of hormones, measure neural activity. The reason for doing all of these measurements is to look at the genetic determinants not only of blood pressure but also the genetic determinants of those factors that are involved in regulation of blood pressure."

Participants receive stipends for the outpatient visit and for the inpatient stay. "They also get a fair amount of medical information about themselves," said Dr. Kotchen, "such as blood pressures and blood tests, cardiograms, renal function, and blood cholesterol. We make all of that information available to them, or their physicians, with their permission.

"The most consistent incentive that we hear from people who volunteer is that they're not doing it so much for themselves as for their children and grandchildren. Perhaps as we learn more about the causes of hypertension, we may be able to develop more effective strategies for preventing it. That will be benefit the next generation."

Dan Ullrich
HealthLink Contributing Writer

MCW Health News presents up-to-date information on patient care and medical research by the physicians of the Medical College of Wisconsin.