Genes May Sway Blood Pressure Drugs' Effectiveness

Finding could lead to more tailored antihypertensive drug treatment

FRIDAY, Sept. 23, 2005 (HealthDay News) -- The fact that the effectiveness of blood pressure medications varies between patients has been long known, but little understood.

Now, researchers say they've found a genetic link that seems to explain at least some of this effect.

"We discovered a region in chromosome 2 that is linked to a specific type of high blood pressure which doesn't respond to two commonly used blood pressure medications," namely ACE inhibitors and beta blockers, said lead researcher Sandosh Padmanabhan, a specialist registrar at the British Heart Foundation in Glasgow, Scotland.

This finding brings researchers a step closer to developing targeted therapies for patients with high blood pressure, according to the report. Identifying genes that determine a person's response to blood pressure medications is critical for more tailored, effective therapies and for understanding the cause of the disease.

"Knowing this, doctors can start patients on medications with some confidence that the medications they are giving will work," Padmanabhan explained.

The report was presented Friday at the American Heart Association's annual high blood pressure research conference, in Washington, D.C.

About 65 million Americans have high blood pressure, and some 25 percent of them will continue to have poor blood pressure control even though they are taking antihypertensive medications, according to the American Heart Association.

In their study, Padmanabhan's team collected data on 2,142 white families with severe hypertension. They noted what drugs were taken, and measured blood pressure after treatment. The researchers found 89 sibling pairs who did not respond to angiotensin-converting enzyme (ACE) inhibitors and beta blockers, and another 76 pairs who did not respond to calcium channel blockers and diuretics.

Using DNA samples from these people, Padmanabhan's group was able to locate an area on chromosome 2 that appears to be involved in causing high blood pressure in people who do not respond to ACE inhibitors and beta blockers.

Blacks typically have salt-sensitive high blood pressure that does not respond to ACE inhibitors and beta blockers, Padmanabhan said. A recent study showed that high blood pressure in blacks can be traced to this same chromosomal region, he noted.

"We found it in Caucasians in the exact same region, but only in a subset of Caucasians who do not respond to ACE inhibitors and beta blockers," Padmanabhan said.

This area appears to be involved in a specific type of hypertension, Padmanabhan said. "If we can pinpoint the genes we would be able to predict those who would respond or not respond to ACE inhibitors and beta blockers. These people can be started on alternative therapy, which will work faster," he said.

One expert thinks the finding is useful, but may not impact the problem of uncontrolled high blood pressure.

"Studies such as this will help our understanding of why patients respond to one therapy or the other," said Dr. Vasilios Papademetriou, a professor of medicine at Georgetown University. "Do not hold your breath, however, that the issue of uncontrolled hypertension will be significantly impacted."

Identifying genes that are implicated in drug resistance will make it easier to treat certain patients by avoiding those therapies, but this is only part of the problem, he said. All the other issues that lead to poor control of hypertension still need to be taken under consideration, including patient compliance, patient and doctor education, the cost of medicines, and testing and side effects, Papademetriou said.

"In short, yes, this is a step forward and a very interesting development from the scientific point of view, but many other variables need to be sorted out before we approach reasonable blood pressure control in the population," Papademetriou added.

More information

The American Heart Association can tell you more about high blood pressure.

SOURCES: Sandosh Padmanabhan, Ph.D., specialist registrar, British Heart Foundation Glasgow, Cardiovascular Research Centre at the University of Glasgow, Scotland; Vasilios Papademetriou, M.D., professor, medicine, Georgetown University, Washington, D.C.; Sept. 23, 2005, presentation, American Heart Association's Council for High Blood Pressure Research, annual fall conference, Washington, D.C.
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