An international research team has identified a number of unsuspected genetic
variants associated with systolic blood pressure (SBP), diastolic
blood pressure (DBP), and hypertension (high blood pressure), suggesting
potential avenues of investigation for the prevention or treatment
of hypertension. The research was funded in part by the National
Heart, Lung, and Blood Institute (NHLBI) of the National Institutes
of Health and by several other NIH institutes and centers.
The analysis of over 29,000 participants is being presented at the American Society
of Hypertension, Inc. scientific meeting on May 8, 2009, and is
published online in the journal Nature Genetics on May 10, 2009.
"This study provides important new insights into the biology of blood pressure
regulation and, with continued research, may lead to the development of novel
therapeutic approaches to combat hypertension and its complications," said NHLBI
Director Elizabeth G. Nabel, M.D.
About 1 in 3 adults (approximately 72 million people) in the United States has
high blood pressure. Hypertension can lead to coronary heart disease, heart failure,
stroke, kidney failure, and other health problems, and causes over 7 million
deaths worldwide each year.
Blood pressure has a substantial genetic component and hypertension runs in families.
Previous attempts to identify genes associated with blood pressure, however,
have met with limited success.
In a genome-wide association study (GWAS), researchers scanned millions of common
genetic variants of individuals from the Cohorts for Heart and Aging Research
in Genomic Epidemiology (CHARGE) consortium to find variants associated with
blood pressure and hypertension. This extensive resource includes white men and
women from the Framingham Heart Study, Atherosclerosis Risk in Communities study,
Cardiovascular Health Study, the Rotterdam Study, the Rotterdam Extension Study,
and the Age, Gene/Environment Susceptibility Reykjavik Study.
The investigators identified a number of genetic variants or single-nucleotide
polymorphisms (SNPs) associated with SBP, DBP, and hypertension. When they jointly
analyzed their findings with those from the GWAS of over 34,000 participants
in the Global BPgen Consortium (whose results are presented in an accompanying
paper in the same issue of Nature Genetics), they identified 11 genes showing
significant associations across the genome: four for SBP, six for DBP, and one
"Large scale genome-wide association studies are providing a number of important
insights into identifying genes that play a role in diseases with major public
health impact," said Dr. Daniel Levy, first author of the study and director,
the NHLBI’s Framingham Heart Study and Center for Population Studies. "We have
identified eight key genes, few of which would have been on anyone’s short list
of suspected blood pressure genes until now."
The international research team included Cornelia M. van Duijn, Ph.D., Erasmus
Medical Center, Rotterdam, the Netherlands; Aravinda Chakravarti, Ph.D., Johns
Hopkins University; Bruce Psaty, M.D., Ph.D., University of Washington; and Vilmundur
Gudnason, M.D., Ph.D., Icelandic Heart Association, Kopayogur, Iceland.
The blood pressure genes include ATP2B1 which encodes PMCA1, a cell membrane
enzyme that is involved in calcium transport; CACNB2, which encodes part of a
calcium channel protein; and CYP17A1 which encodes an enzyme that is necessary
for steroid production. One detected variant is within the gene SH2B3 and has
been associated with autoimmune diseases, hinting that pathways involved with
the immune response may influence blood pressure.
Blood pressure is measured in millimeters of mercury (mm Hg), and expressed with
two numbers, for example, 120/80 mm Hg. The first number (systolic pressure)
is the pressure when the heart beats while pumping blood. The second number (diastolic
pressure) is the pressure in large arteries when the heart is at rest between
Researchers found that the top 10 gene variants, or SNPs, for systolic and diastolic
blood pressure were each associated with around a 1 and 0.5 mm Hg increase in
systolic and diastolic blood pressure, respectively. The prevalence of hypertension
increased as the number of variants increased.
People who carry very few blood pressure genetic risk variants have blood pressure
levels that are several mm Hg lower than those who carry multiple risk variants.
In practical terms this is enough to increase the risk for cardiovascular disease.
A prolonged increase in DBP of only 5 mm Hg is associated with a 34 percent increase
in risk for stroke and a 21 percent increase of coronary heart disease.
The research was funded by NHLBI grants and contracts and was also supported
by the National Human Genome Research Institute (NHGRI), National Center for
Research Resources (NCRR), National Institute on Aging (NIA), and the NIH Roadmap.
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Part of the National Institutes of Health, the National Heart, Lung, and Blood
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