LDS Hospital researchers hope to figure out the genetics of high cholesterol so that prevention efforts and treatment can be tailored for individuals.
The National Institutes of Health awarded the hospital's Cardiovascular Research Department a four-year, $2.3 million grant to undertake the unique and potentially groundbreaking study, which will begin immediately using genetic information already collected from more than 10,000 heart patient volunteers who have been tested or treated in the hospital's cardiac cath lab.
The Intermountain Heart Collaborative Study is the largest clinical genetic study and database of heart patients in the world.
High cholesterol is just one risk factor long recognized as contributing to heart disease, which is the leading killer in Utah and across the nation. And both cholesterol and heart disease have familial — or genetic — factors, though they're not well understood, said Dr. Jeffrey Anderson, professor of medicine at the University of Utah Medical School and associate chief of cardiology at LDS Hospital.
Anderson believes the grant recognizes both the importance of understanding the genetic underpinnings of heart disease and the role Utahns' "great record of voluntarism" can play in medical discovery. More than a decade ago, LDS Hospital established a databank with DNA samples from people who had come through the cardiology cath lab because of heart disease. Because of the source of the DNA, the researchers also know some of the medical outcomes, such as whether the DNA donor has died of heart disease.
Part of the NIH grant will be used to go back and test the collected samples for six genes that are already known to impact cholesterol metabolism, to look for variants in those genes and determine how they work and if or how they contribute to heart disease. They're not rare mutations but common genetic changes, said Anderson, lead investigator for the study.
The goal is to build a "genetic risk score that might help us better understand the genetics of risk for heart disease that we so poorly understand now," he said. To do that, the variants most likely involved would be analyzed and ranked in some way so they become standard markers of risk.
In the next year, researchers will also recruit folks from two other groups to donate samples to the bank: people who don't have a diagnosed history of heart disease and a separate category of those with a strong family history of early heart disease. With those three groups — those with known heart disease, those who apparently don't have heart disease and those with a family predisposition to it — much can be learned, Anderson said. For those in families where men developed heart disease at 55 or younger and women at 65 or younger, genetic factors are likely to be involved.
The researchers are especially interested in getting blood samples and a health survey from people who belong to ethnic minorities, who are very underrepresented in the existing DNA bank.
It's part of a growing trend to use genetic testing as a disease prevention tool, not just a diagnostic tool, Anderson said. An emerging field called pharmacogenetics ties in closely. In pharmacogenetics, therapies and specific medications could be created that target specific genetic variations or findings.
The information gathered for the database and study is all confidential, Anderson said.
LDS Hospital researchers are working with researchers from the U.'s cardiovascular genetics program and genetic epidemiologic division and will also use the expertise of Idaho Technology, a Utah-based biotech company responsible for many of the instruments and reagents used in research and applied fields.
Among the researchers are co-principal investigator John Carlquist, Ph.D., director of the molecular pathology laboratory at LDS Hospital; Dr. Paul Hopkins and Steven Hunt, Ph.D., from the U.'s cardiovascular genetics program; Dr. J. Brent Muhlestein and Benjamin Horne, from LDS Hospital Cardiology Research; and Lisa Cannon-Albright, Ph.D., and Nicola Camp, Ph.D., from the U. Genetic Epidemiology Division.
Families with a history of early heart disease can volunteer to participate by calling 581-3888. Hopkins is heading that part of the study. Individuals who are, as far as they know, heart healthy and would be willing to donate a tube of blood and fill out a questionnaire are asked to call 408-5902.
E-mail: lois@desnews.com