"Knowing these gene-drug combinations will help doctors prescribe medication that an individual will be most likely to respond to," said lead author Sharon Kardia, Ph.D., associate professor and director of the University of Michigan Public Health Genetics Program.
"This is an important finding given the tremendous variation among people's responses to blood pressure-lowering medications," added co-author Stephen T. Turner, M.D., professor of medicine in the Division of Hypertension at the Mayo Clinic in Rochester, Minn. "Doctors and patients have to go through often frustrating trial-and-error periods to find the best medication."
Investigators are conducting these studies as part of the National Heart, Lung and Blood Institute's Family Blood Pressure Program, a large collaborative research effort aimed at identifying genes that contribute to high blood pressure. The study involved 1,162 hypertensive white men and women from Rochester, Minn. Hypertension is systolic blood pressure (the top number in a blood pressure reading) of 140 millimeters of mercury (mmHg) or higher, or diastolic pressure (bottom number) of 90 mmHg or higher. Pre-hypertension is 120-139/80-89 mmHg. The researchers noted what drugs the study participants were taking to control their hypertension and measured their blood pressure after treatment. The researchers also screened participants for specific genes shown in previous studies to affect blood pressure, including the adducin 2 (ADD2) and solute-carrier 9A (SLC9A2).
They found ADD2 and SLC9A2 were associated with blood pressure. The researchers identified a single nucleotide polymorphism, or SNP, in ADD2 that was associated with lower average systolic blood pressure in hypertensive people treated with beta-blockers only. Participants with the ADD2 gene who were taking beta blockers had an average systolic blood pressure of 133 mmHg, compared to 158 mmHg for participants not taking medications and 146 mmHg for those treated with diuretics only. Overall, blood pressure in patients taking beta-blockers did not differ from those taking diuretics. Only patients carrying ADD2 had significantly higher systolic pressure in the not treated and diuretic groups.
Participants with a SNP in SLC9A2 and being treated with beta-blockers averaged 72 mmHg diastolic blood pressure, compared to 93 mmHg for those with the same SNP taking only calcium channel blockers and 84 mmHg for people only on RAS inhibitor therapy.
"This response variation probably stems from differences in underlying mechanisms that control blood pressure in individuals," Kardia said. "One person might have high blood pressure due to their kidneys reabsorbing too much sodium. That patient, as a result, would probably respond best to a diuretic." Knowing about these genes and their variants will help researchers predict which people are at greater risk for high blood pressure; identify and develop new treatments to lower blood pressure; identify who is at risk for conditions caused by high blood pressure, such as stroke; and help target treatment so that patients get the most effective medication to treat their high blood pressure, said co-author Eric Boerwinkle, Ph.D., professor and center director at the University of Texas Health Science Center in Houston who is head of the Family Blood Pressure Program.
"These findings need to be confirmed in controlled clinical trials," Kardia said. "If confirmed, this would be another piece of the puzzle explaining why high blood pressure occurs and how best to control it."