Table of Contents
Genetic Variation Affects Impact
of Hypertension Medication
Research takes step toward tailoring drug therapies for individual patients
Eric Boerwinkle, Ph.D., and Lorraine Frazier, D.S.N., collaborate on research into genetic effects on hypertension medication.
Photo by Pamela Lewis
Minimal variation in two genes affects how African-American women respond to the most common blood pressure medication, a research team led by University of Texas Health Science Center at Houston scientists has found.
Women with specific versions of the two genes have an average reduction of up to 24 millimeters of mercury (mmHg) in their systolic blood pressure when treated with the diuretic hydrochlorothiazide, researchers report in the January issue of The Pharmacogenomics Journal, a publication of the Nature Publishing Group.
Researchers from two of the UT Health Science Center’s schools, with colleagues at Mayo Clinic in Rochester, Minn., and Emory University in Atlanta, studied the impact of variation in five genes that are integral to a system used by the kidneys to monitor and increase blood pressure. The Renin Angiotensin Aldosterone (RAA) system naturally counters the blood pressure-lowering effects of taking a diuretic.
The team examined the connections between the diuretic medication and RAA genetic variation by studying 255 hypertensive African-Americans and 246 hypertensive non-Hispanic whites who were placed on the medication in controlled conditions.
“One important conclusion from this study is that even as genetic information is applied to better customize drug therapies we will still need to take into account gender and ethnic background as well as genetic variation,” said lead author Lorraine Frazier, D.S.N., associate professor of nursing at the UT School of Nursing at Houston.
No statistically significant impact was found on systolic blood pressure among the male patients or among white females.
For African-American women, a single point of variation known as a single nucleotide polymorphism (SNP) on the angiotensinogen gene and another SNP on the angiotensin II receptor gene affected their response to the medication.
Statistical analysis showed the impact of the two points of variation is independent and additive, Frazier said. There was no evidence of interaction between them. Their effect on African-American women’s response to the diuretic also remained significant even after accounting for other blood pressure risk factors such as body type, age and baseline blood pressure.
Hypertension – consistently high blood pressure of 140/90 – afflicts an estimated 50 million Americans, raising their risk for cardiovascular disease, stroke and renal failure. Various medications are used alone or in combination to control hypertension.
“These results are an important addition to our understanding of why the effectiveness of a blood pressure medication can vary so much from patient to patient,” said senior author Eric Boerwinkle, Ph.D., director of the Human Genetics Center at both the UT School of Public Health at Houston and at the university’s Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases.
“The potential to more precisely tailor drug therapies to individual patients is one of the most promising applications of our rapidly expanding knowledge of the human genome,” said Boerwinkle, who is also a faculty member in the UT Graduate School of Biomedical Science at Houston.
— By Scott Merville, Public Affairs