Lab Canada

Canadian and US research tracks genetics of hypertension

Montreal, QC – Researchers today announced that they have created a genetic database that offers hope for improved diagnosis and treatment of hypertension, a condition that affects about five million adult Canadians.

A team led by Dr Pavel Hamet of Montreal, in partnership with Dr Daniel Gaudet in Saguenay, studied 120 French-Canadian families in the 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. This study was primarily funded by the US National Heart, Lung, and Blood Institute (NHLBI), through the specialized centers of research (SCOR) program.

Dr Hamet’s work is further supported by the Institute of Circulatory and Respiratory Health (ICRH) of the Canadian Institutes of Health Research (CIHR), the Heart and Stroke Foundation of Canada (HSFC), the Canada Foundation for Innovation, and Valorisation Recherche Qubec. The study is being published in the prestigious American Journal of Human Genetics in May 2005.

“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, who is lead investigator, director of research at the Centre hospitalier de l’Universit de Montral (CHUM). “By genetically identifying the underlying cause, treatment could become more tailored to the individual, the family and even entire ethnic groups.”

“The potential benefits of Dr Hamet’s findings to patients and to the health care system are considerable,” says Dr Bruce McManus, scientific director of CIHR’s Institute of Circulatory and Respiratory Health. “In the future this work may help us determine the likelihood of an individual developing hypertension and a target gene for treatment.”

Currently, each anti-hypertension medication works in only about 50% of patients. As a result doctors may have to prescribe several medications, and time is lost as doctors work to find the right combinations for each patient. Anti-hypertensive medications can also cost the healthcare system over $1,500 a year per person and some people are not getting the full benefits of their medication, which could be achieved if their treatment targeted the appropriate genes responsible.

Dr Hamet’s research focuses on 120 French-Canadian families – 900 individuals – living in the Saguenay-Lac-St Jean region. Many of these families are direct descendants of the original settlers who came to New France 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 Grard Bouchard and his team at the Universit du Qubec Chicoutimi (UQAC). Together, they have developed a computerized demographic and genealogical register (the BALSAC Database) covering the majority of the Quebec 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.

“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.”

The success of these research findings are the result of a team effort between CHUM and the Chicoutimi Hospital (both Universit de Montral) and researchers from five universities: Ecole Polytchnique de Montral, UQAC, McGill, University of Ottawa, and MIT. Significant contributions also came through a long standing collaboration with researchers of the Medical College of Wisconsin through the SCOR Program directed by Dr Allen W Cowley Jr.

“Hypertension is a common, complex disease in an area where past successes were mainly restricted to simple, monogenic diseases,” comments Prof Cowley. “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.”

The leadership of Ettore Merlo in bio-informatics and Daniel Gaudet, from the Universit de Montral Community Genomic Medicine Centre in Chicoutimi were also critical to successfully deciphering this disease.

“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,” says Dr Hamet.

Dr Hamet’s work is supported through the gene-environment interactions in circulatory and respiratory health program led by ICRH and HSFC. In 2002, his team was awarded an Interdisciplinary Health Research Team (IHRT) grant for a total of $2.6 million over five years. The aim of this research is to better understand genetic and environmental interactions – something that is already happening after three years, and should lead soon to the development of targeted and preventive interventions in cardiovascular disorders.