ShareThisResearchers are working aggressively to find ways to use our genes to guide our medical care.
While scientists have been identifying genetic markers for diseases for decades, the connections mostly make a difference only when a condition is caused by the malfunction of a single gene.
And there are more than 6,000 known single-gene disorders, including cystic fibrosis, sickle-cell anemia, Huntingdon's disease and hereditary hemachromatosis (excessive iron buildup in blood cells).
But with some exceptions in cancer care, researchers have had difficulty making discoveries linking multiple genes to a disease relevant to treatment, or preventive steps.
"For the vast majority of (genetic) risk assessments, the increased risk of an individual developing the disease in question is modest. ... And in few such conditions are there specific effective interventions to diminish the risk," said Dr. James Evans, professor of genetics and medicine at the University of North Carolina School of Medicine.
Most genetic studies simply didn't tell doctors much else about the people carrying the gene.
The National Human Genome Resource Institute last year announced a $31 million effort to start closing those knowledge gaps by matching about 300 genetic variants linked to common diseases with individuals' biological and physical characteristics.
So, if a person carries X gene variant, just what is his or her weight, cholesterol level, blood-sugar level or bone density? And how does lifestyle -- diet, smoking and drinking habits and exercise levels -- possibly interact with the gene to influence the onset or severity of disease?
After four years, the institute expects to have data from about 40,000 people, giving a solid base of how bodies and gene variants are arranged.
Many other research efforts are focused on how people with different gene variations respond to vitamins or medicines.
For instance, scientists at the University of California-Berkeley have been testing human gene variants transplanted into yeast cells to see how certain enzymes respond to vitamins.
"Our studies have convinced us that there is a lot of variation in the population in these enzymes," said researcher Nicholas Marini. "I wouldn't be surprised if everybody is going to require a different optimal dose of vitamins based on their genetic makeup" both to prevent disease and to optimize physical fitness in athletes or soldiers.
One of the more advanced projects to match genetics with dosing is reported this week in The New England Journal of Medicine, showing that the amount of the blood-thinner warfarin prescribed to a patient can be pinpointed with a formula that includes data on which version of two different genes he or she carries.
Each year, 2 million Americans start taking warfarin due to a heart condition or other circulatory disease. But each person responds differently to the drug, so doctors typically have to experiment with doses over several weeks or months to get the right amount. This is both tedious and dangerous, since someone taking too much can suffer uncontrolled bleeding, while someone getting too little remains at risk for dangerous blood clots.
To explore the variations in the two genes -- one affects how the liver activates and excretes the drug, the other activates vitamin K, essential to blood clotting -- an international team from 21 institutions in nine nations collected data from more than 5,700 people.
Researchers found that the right dose for one person can be as much as 10 times greater than for another, but that a formula that includes traditional clues, like height, weight and ethnic background, along with the genetic information, can pinpoint the correct dose to within a few milligrams a week of the ideal.
"We're hoping that our research will help clinicians get it right on the first try," said Dr. Russ Altman, a professor of medicine and genetics at Stanford University who helped organize the study.
Next, several groups in Europe and the United States are setting off clinical studies comparing outcomes from several thousand patients prescribed warfarin, with half getting their dose set using traditional guidelines alone, the others based on the new genetic formula.
On the Net: http://www.nejm.org
(Reach Lee Bowman at bowmanl(at)shns.com.)
THE MEDICAL JOURNAL
