Genetics Influence Blood Pressure Medications

TUESDAY Jan. 22, 2008 -- A person's genetic make-up seems to influence how he or she reacts to certain hypertension medications.

In the future, being able to match genes with medications may help save a patient's life, experts predict.

"This is potentially a very, very important observation. It's a large study with hard clinical endpoints," said Dr. Joshua M. Hare, chief of cardiology at the University of Miami Miller School of Medicine. "This is a beautiful example of what we anticipate personalized medicine to be," said Hare, who was not involved in the research.

Another expert agreed. Dr. Jeffery Vance, professor at the Miami Institute for Human Genomics, said that "This is where medicine is going. It's important that we've got big clinical trials [showing this]. They cost a lot of money but this shows that it's clearly worth it."

The gene variant identified in the new study is likely to be just one of several that play a role in hypertension, also known as high blood pressure.

"Hypertension is such a complex disease. There are many different mechanisms that help us regulate our blood pressure so we would not expect any one gene to have a really large effect for [such] a common condition like hypertension," noted study senior author Donna K. Arnett, professor and chair of the University of Alabama at Birmingham's department of epidemiology. "That we found this effect is important because we didn't think we would ever be able to do pharmacogenetics, given the complexity of hypertension."

According to background information with the study, published in the Jan. 23 issue of the Journal of the American Medical Association, some 65 million people in the United States have hypertension. But only about two-thirds have their condition under control. Uncontrolled hypertension can lead to such problems as heart attack and stroke.

Previous studies have shown that the presence of certain gene characteristics can predict response to treatments such as ACE inhibitors, which are drugs used to control hypertension. But this information hasn't been adopted widely by doctors.

The new study focused on the NPPA (atrial natriuretic precursor A) gene, which is involved in forming atrial natriuretic polypeptide, which acts as a diuretic.

Specifically, the study authors wanted to see if people with hypertension and two different NPPA genotypes (known as NPPA G664A and NPPA T2238C) responded differently to different medications.

In all, 38,462 people with hypertension underwent genotyping [genetic testing] and were randomly assigned to receive a diuretic (chlorthalidone) or one of the following three drugs: a calcium channel blocker (amlodipine); an angiotensin converting enzyme inhibitor (lisinopril); or an alpha-blocker (doxazosin).

People with the more common subtype of the NPPA gene responded better to the calcium channel blocker than the diuretic. There were no differences in response between the diuretic and the other two drugs studied, the researchers said.

People with the other genotype fared better on the diuretic.

"Eventually we should be able to utilize prescreening for treatment to determine which drug you may respond best to," Arnett said. "This is a small but important step towards personalized medicine."

Posted: January 2008


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