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Gene
variations associated with effectiveness of
Blood Pressure medications
Newswise — Patients with hypertension and certain
gene variations experienced varying results
with some blood pressure medications,
suggesting matching a patient’s genotype
with certain hypertension medications could
result in more favorable outcomes, according
to a study in the January 23 issue of JAMA.
Approximately 71 million individuals in the
United States have one or more types of
cardiovascular disease (CVD), of whom at
least 65 million have hypertension.
Although control of hypertension has been
improving in recent years, among those
treated, only about two-thirds have their
hypertension controlled, according to
background information in the article.
Seeking ways to reduce CVD illness and death by
tailoring treatment to a patient’s
particular genotype has been an area of
research, but results have yet to yield
therapeutic choices for the clinical
setting.
Amy I. Lynch, Ph.D., of the University of
Minnesota, Minneapolis, and colleagues
conducted a study to examine whether
patients with hypertension with minor NPPA (atrial
natriuretic precursor A) genotypes (NPPA
G664A and NPPA T2238C) randomized to the
diuretic chlorthalidone had different
outcomes for CVD measures than patients who
were randomized to other classes of
antihypertensive medication.
Previous research has suggested that the NPPA
gene may influence the effectiveness of some
antihypertensive drugs.
The study included 38,462 participants with
hypertension from ALLHAT (Antihypertensive
and Lipid Lowering Treatment to Prevent
Heart Attack Trial), a multicenter
randomized clinical trial conducted in the
United States and Canada. Genotyping was
performed from February 2004 to January
2005.
Participants were randomly assigned to receive a
diuretic (chlorthalidone; n = 13,860), a
calcium channel blocker (amlodipine; n =
8,174), an angiotensin-converting enzyme
(ACE) inhibitor (lisinopril; n = 8,233), or
an alpha-blocker (doxazosin; n = 8,195).
Follow-up averaged 4.9 years.
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
chlorthalidone (diuretic) group with the
amlodipine (calcium channel blocker) group,
and for stroke when comparing the
chlorthalidone group with those receiving
amlodipine or lisinopril (ACE inhibitor). T
he 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 chlorthalidone compared with
those assigned to amlodipine (and the
amlodipine group plus the lisinopril group
for stroke), while those in the
chlorthalidone group with the TT genotype
had higher risk of disease and/or death than
those assigned to amlodipine.
“We also observed a pharmacogenetic association
of NPPA T2238 on change in systolic and
diastolic blood pressure 6 months after
treatment randomization in a similar
direction: generally, minor C allele
carriers had greater reductions in blood
pressure when randomized to chlorthalidone
vs. either lisinopril or doxazosin relative
to those with the common TT genotype,” the
authors write.
“This study demonstrates the importance (and
sometimes paradoxical findings) of
pharmacogenetic research; for example, while
minor NPPA T2238C allele carriers (as well
as the entire study population viewed as a
whole) may have had more favorable outcomes
when randomized to a diuretic (chlorthalidone),
participants with the most common genotype (TT)
responded better when assigned to a calcium
channel blocker (amlodipine) for some
clinical outcomes.”
“Further research is needed to determine the
optimal approach for personalizing
antihypertensive medication treatment
regiments according to genotype information
and for achieving the best possible clinical
outcomes,” the researchers conclude.
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