Genetics May Hold Key to Blood Pressure Treatment

Study to determine if genes influence medications' effects

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HealthDay Reporter

WEDNESDAY, Sept. 24, 2003 (HealthDayNews) -- Will genetic tests one day help determine the best medication for someone with high blood pressure?

U.S. researchers hope to answer that question with a new study that will take the better part of a decade. But at least one expert points out that many factors, including genetics, can influence hypertension. So it might be difficult to arrive at a single test.

The new research was discussed Sept. 24 at the American Heart Association's 57th annual High Blood Pressure Research Conference in Washington, D.C. Those involved hope it will lead to better treatments for one of the nation's leading causes of heart attack and stroke, says study leader Sharon Kardia, director of the University of Michigan's Public Health Genetics Program.

High blood pressure killed 44,619 Americans in 2000 and contributed to the deaths of about 118,000, the heart association says.

The study will examine the effect of two different blood pressure medications on people who carry two different genes associated with hypertension. One of the genes, designated ADD2, appears to make blood pressure drugs called beta blockers work more effectively in people who carry it. The other gene, designated SLC9A2, appears to be associated with more effective results with a thiazide diuretic blood pressure drug.

A total of 1,200 people who carry one or another of the two genes are being enrolled in the study, says study leader Dr. Stephen T. Turner, a professor of medicine at the Mayo Clinic in Rochester, Minn. Half will get a beta blocker, the other half will get a thiazide diuretic. They will be followed for seven to eight years to see whether genetic makeup affects how well the drugs work.

The study, funded by the National Heart, Lung, and Blood Institute, comes in response to observations that carriers of a certain gene did better with certain kinds of high blood pressure medications. For example, carriers of a specific form of the ADD2 gene who were given a beta blocker had an average systolic blood pressure that was 20 points lower than those who were given a diuretic.

"The inference would be that people with these genotypes respond more favorably if put on those specific drugs," Turner says.

But that inference has to be tested carefully because observational studies can be misleading, he adds. One prime example is the lesson learned about hormone replacement therapy for menopausal women, he adds.

"Based on observational data, it was inferred that women who took hormone replacement therapy had favorable effects from those medications," Turner says. "But when you went out and did a prospective study, low and behold, it didn't work out that way."

A portion of the Women's Health Initiative was halted in July 2002 after results showed estrogen combined with progestin increased the risk of invasive breast cancer in menopausal women.

Nevertheless, the new study could help explain some of the complexities of high blood pressure incidence and treatment, Turner says. Previous studies have shown that blacks respond better to thiazide diuretic treatment than whites, he notes, and the suspicion is that this could be because they are more likely to carry the SLC9A2 gene. To test that theory, the study will include equal numbers of blacks and whites.

But even if the study reaches all its goals, it will be one small step in the complex field of hypertension research, says study leader Eric Boerwinkle, director of the Human Genetics Center at the University of Texas Health Sciences Center.

"Hypertension is a complex process of many genes interacting with many environmental factors to affect the risk of heart attack or stroke," Boerwinkle says. The best estimate is that there may be dozens of genes involved, and that overall, genetics accounts for about 35 percent of risk, he says.

"There are also differences in gene activity," Boerwinkle says. "The idea is that we are looking at some genes that influence blood pressure in young people, genes that influence blood pressure as you get older, and genes that have an effect on the clinical outcome if you have hypertension."

So it appears impossible to develop one single genetic test that would pinpoint individual risk of high blood pressure, Boerwinkle says. "What we will see is a combination of tests of genetic risk factors and classic risk factors," he explains.

Earlier this week, researchers in Iceland said they had identified a gene associated with increased risk for ischemic stroke. People with the PDE4D gene are three to five times more likely to suffer this type of stroke, where blood flow to the brain is restricted. Efforts to reduce the risk of these strokes by targeting drugs at that gene have begun, the researchers say.

More information

The American Heart Association has more on high blood pressure and the factors that contribute to it.

SOURCES: Sharon Kardia, Ph.D., director, University of Michigan Public Health Genetics Program, Ann Arbor; Stephen T. Turner, M.D., professor, medicine, Mayo Clinic, Rochester, Minn.; Eric Boerwinkle, Ph.D., director, Human Genetics Center, University of Texas Health Sciences Center, Houston; Sept. 24, 2003, presentation, American Heart Association's 57th Annual High Blood Pressure Research Conference, Washington, D.C.

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