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Genes may sway blood-pressure drugs' effectiveness



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The fact that the effectiveness of blood-pressure medications varies between patients has long been known, but little understood.

Now researchers have 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, says 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, the report says. 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," Padmanabhan says, "doctors can start patients on medications with some confidence that the medications they are giving will work."

The report was presented on Sept. 23 in Washington at the American Heart Association's annual high-blood-pressure research conference. About 65 million Americans have high blood pressure, according to the American Heart Association, and some 25 percent of them continue to have poor blood-pressure control even though they are taking antihypertensive medications.

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 says, and a recent study suggested that high blood pressure in blacks can be traced to this same chromosomal region.

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

This area appears to be involved in a specific type of hypertension, Padmanabhan adds.

"If we could pinpoint the genes," he says, "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."

Dr. Vasilios Papademetriou, a professor of medicine at Georgetown University in Washington, thinks the finding is useful, but doesn't expect it to solve 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," Papademetriou says.

"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, Papademetriou says, but this is only part of the problem. 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.

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

(The HealthDay Web site is at http://www.HealthDay.com.)

c.2005 HealthDay News

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