A new study has identified the first common gene variants associated with an increased incidence of hypertension - a significant risk factor for heart attack, stroke and kidney failure.
The report receiving early online release in the journal Nature Genetics identifies variants in genes for proteins involved with cardiovascular response to stress that also appear to influence blood pressure levels, an association previously seen in animals but not demonstrated in humans.
"It's well known that hypertension can run in families, and a few rare genetic syndromes that raise blood pressure have been identified. But the common genetic basis for the type of hypertension that affects a billion individuals around the world has been very difficult to establish," says Christopher Newton-Cheh, MD, MPH of the Massachusetts General Hospital (MGH) Center for Human Genetic Research and Cardiovascular Research Center, first author of the Nature Genetics report.
To search for hypertension-associated variants, the investigators focused on two genes called NPPA and NPPB that are involved in the production of atrial and B-type natriuretic peptides (ANP and BNP) - proteins known to relax blood vessels and to be involved in the excretion of dietary sodium. Animals in which both copies of NPPA have been knocked out are hypertensive, and even those with a single functional copy will develop hypertension on a high-sodium diet.
The overall study involved analyzing genetic data from almost 30,000 individuals. The researchers first screened 1,700 participants in the Framingham Heart Study for 13 common variations - called single-nucleotide polymorphisms (SNPs) - in the NPPA and NPPB genes, looking for any correlation with levels of ANP and BNP. SNPs identified in that first stage were validated in three other study groups, including participants from Sweden and Finland; and variants associated with changes in natriuretic peptide levels were then tested in the same individuals for any association with blood pressure levels.