New Genetic Information Could Improve High Blood Pressure Diagnosis, Treatment

Newswise — Canadian and U.S. researchers at the Medical College of Wisconsin today announced important new information on the genetics of hypertension offering hope for improved diagnosis and treatment of high blood pressure, a condition that affects millions of North Americans.

The study is reported in the May issue of American Journal of Human Genetics. This study was primarily funded by the U.S. National Heart, Lung, and Blood Institute, through the Specialized Centers of Research (SCOR) Program. The Medical College of Wisconsin was the recipient of an $8.2 million SCOR grant in 1996, and renewed in 2001 for $11.3 million, which helped fund this study. It is directed at the Medical College by Allen W. Cowley, Jr., Ph.D., professor and chairman of physiology. Dr. Cowley and Theodore Kotchen, M.D., associate dean for clinical research and professor of medicine at the Medical College, have coauthored the study with the lead author, Pavel Hamet, M.D., director of research Centre Hospitalier de L'Universite de Montreal

Dr. Hamet, in partnership with Dr. Daniel Gaudet in Saguenay, Quebec, studied 120 French-Canadian families in the isolated Saguenay-Lac St. Jean region in Quebec for genetic markers for hypertension on their chromosomes. Researchers found 46 significant chromosomal areas associated with hypertension and its cardiovascular and metabolic consequences.

"We have taken an important step towards the day when we will be able to diagnose the genetic cause of an individual's hypertension by simple blood test," says Dr. Hamet. "By genetically identifying the underlying cause, treatment could become more tailored to the individual, the family and even entire ethnic groups."

According to Dr. Cowley, "The study results clearly demonstrate the genetic complexity of functional elements that are involved in hypertension. Hypertension is a common, complex disease in an area where past successes were mainly restricted to simple, monogenic diseases. Choice of this specific population, its comparison with other populations in the United States, detailed phenotyping and multidisciplinary approach led to the success of this study."

Dr. Cowley's studies of inbred strains of rats have provided important clues for identifying genes of high blood pressure in humans. Since rats contain 95 percent of the same genes as humans, they provide the ability to study the relationships of genes to allow the complex biological systems that are involved in the regulation of blood pressure.

The researchers designed similar studies in the French-Canadian population and in the African American population in Milwaukee that is being studied by Dr. Kotchen"We will use the African American population to confirm the results from the French Canadian group to see if it can be replicated in a genetically distinct population. We will also further refine the areas of linkages found in the French-Canadians' DNA," says Dr. Kotchen.

By using three distinct populations, two in humans and one in rats, the researchers are able to use sophisticated testing and analytical methods to narrow the regions which have been identified to contain genes influencing blood pressure.

Dr. Hamet's research focuses on 120 French-Canadian families " 900 individuals many of whom are from families who are direct descendants of the original settlers who came to Quebec in the 17th century. Their genealogical records from 1680 to the present have been computerized and are available to the researchers through the systematic effort of Prof. Gérard Bouchard and his team at the Université du Québec à Chicoutimi (UQAC). Together, Drs. Hamet and Bouchard have developed a computerized demographic and genealogical register (the BALSAC Database) covering the majority of the Québec population from the 17th through the 20th century. The research team spent two days running tests on each individual studied within the families, examining all forms of cardiovascular function and scanning their genomes. Family members were screened for 250 clinical characteristics and their genome scanned with 400 genetic markers. DNA samples from the first 500 recruited subjects from 97 families were genotyped at the Whitehead Institute in Boston. A total of 46 locations within the human genome were identified containing genes that influence blood pressure, obesity, distribution of body fat, and metabolic traits related to blood lipids, and hormones that control blood glucose such as insulin. Genes determining several or more of these traits, especially those of particular importance in hypertension and obesity, were clustered on four chromosomes.

"We are now in a position to discover which genes are susceptible or resistant to stress, nutrition, or to the socio-economic factors associated with hypertension," says Dr. Hamet. "People in the Saguenay do not have more hypertension than the rest of Canada " it's just that the genes that cause hypertension are easier to find, because the family histories are known. By working in this region, we could take full advantage of the BALSAC Database."

"We have laid the groundwork for the novel concept of a quantitative founder effect, in which a trait determined within a set of families is measurably and quantitatively transmitted throughout generations contributing to a specific component of the disease," concludes Dr. Hamet.

"With this information and the linkage analyses, we are now pursuing detailed gene hunting strategies. This multidisciplinary approach moves us closer to the day when we will be able to diagnose the genetic cause of hypertension in individual by a simple blood test and tailor their most suitable therapy," Dr. Cowley points out.