Genetic Makeup May Affect Blood Pressure Medications

Genetic makeup may impact the effectiveness of medications for high blood pressure, which could help explain why certain drugs work for some people and not for others. The research, published in the Jan. 23 issue of JAMA - the Journal of the American Medical Association - was conducted in part by scientists at The University of Texas School of Public Health.



Barry Davis, M.D., Ph.D.

“This may indicate that down the road we could prescribe treatments better suited to a patient’s individual genetic makeup,” said co-author Barry Davis, M.D., Ph.D., professor of biostatistics and the director of the Coordinating Center for Clinical Trials at The UT School of Public Health. “We have a gene that may affect the efficacy of some antihypertensive treatments.”

High blood pressure or hypertension affects at least 65 million Americans and contributes to heart failure, stroke and heart attack. Medications are often recommended when diet, exercise and lifestyle changes fail to manage this condition. However, only about two-thirds of the people receiving treatment have their hypertension controlled.

Researchers found that slight variants in a gene named NPPA appeared to impact the effectiveness of medications for high blood pressure. For example, diuretics were more effective than calcium channel blockers in treating participants with one variation. But, calcium channel blockers proved more helpful in the care of people with a second variation.

The study involved a genetic analysis of 38,462 people with blood pressure of 140/90 mm Hg or greater or who had been on blood pressure medications. Researchers also tested the impact of genetic variants on two other classes of high blood pressure medications - ACE inhibitors and alpha blockers - in addition to diuretics and calcium channel blockers.

Diuretics reduce blood pressure by lowering the amount of fluid in blood. Calcium channel blockers relax blood vessels. ACE inhibitors prevent the formation of a hormone which causes blood vessels to narrow. Alpha blockers reduce nerve impulses that constrict vessels. These classes of medication are used separately or in combination.

Study participants were initially involved in a landmark investigation based at The UT School of Public Health, which in 2002 established that diuretics – a relatively inexpensive treatment - were “as good or better” than three other classes of medications for high blood pressure during a multi-center, randomized, double-blind clinical trial. The investigation is called ALLHAT - Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial.

“We captured the genetic material or DNA of the participants and we’re using it to test if there are genetically modified responses to drugs, a field of study known as pharmacogenetics,” said Davis, the James W. Rockwell Professor of Public Health. “The goal of pharmacogenetics is to provide individualized treatment guided by genetic information.”

The researchers found evidence of a pharmacogenetic association of the NPPA T2238C variant with coronary heart disease (CHD), stroke, all-cause death, combined CHD, and combined CVD when comparing the diuretic group with the calcium channel blocker group, and for stroke when comparing the diuretic group with those receiving calcium channel blocker or ACE inhibitor.

The association was consistent for all outcomes: those with at least one copy of the minor C allele (alternative form of a gene) had lower risk of disease and/or death when assigned to diuretic compared with those assigned to calcium channel blocker (and the calcium channel blocker group plus the ACE inhibitor group for stroke), while those in the diuretic group with the TT genotype had higher risk of disease and/or death than those assigned to calcium channel blocker.

Davis said additional research should be conducted, including cost analyses before pre-prescription genetic testing is warranted for determining treatment for hypertension.

Other researchers from The UT School of Public Health included: Eric Boerwinkle, Ph.D., the Kozmetsky Family Chair in Human Genetics and director of the Human Genetics Center and Division of Epidemiology; and Charles Ford, Ph.D., associate professor of biostatistics and principal investigator of the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial.

The study received support from the National Heart, Lung and Blood Institute.

Amy I. Lynch, Ph.D., of the University of Minnesota, was lead author on the study titled “Pharmacogenetic Association of NPPA T2238C Genetic Variant With Cardiovascular Disease Outcomes in Patients with Hypertension.”