Large study brings hope for treating genetic causes of high blood pressure


Large study brings hope for treating genetic causes of high blood pressure

A large international study that analyzed genetic data from up to 130,000 people found common variants in 8 regions of DNA are linked to blood pressure levels in humans, raising the hope that these could be targets for new drugs to treat or even prevent high blood pressure.

The study involved over 150 scientists from 93 research centres in the US and Europe and was published online in the 10 May issue of Nature Genetics.

One group of scientists working on the study, including the first and corresponding author, Dr Christopher Newton-Cheh, is based at Massachusetts General Hospital (MGH) in the US. Newton-Cheh is also an assistant professor of Medicine at Harvard Medical School.

Newton-Cheh explained that the study was a "major advance" because it found new genetic pathways that increase our understanding of what causes high blood pressure and raises the possibility that these could be targets for drugs that might treat or even prevent the condition.

6 of the 8 DNA regions have not been tied to blood pressure regulation before, said the researchers.

High blood pressure (hypertension) is a major risk factor for heart attack, stroke, kidney failure and heart failure and can run in families. There are also some rare genetic disorders that raise blood pressure.

But the problem with pinning down the genetics of high blood pressure is that each factor has a small effect, and so you need very large numbers of participants, and you need to look at more than one factor at a time, to get a strong picture of how genes influence blood pressure.

This is essentially what this very large consortium of research centres did. By collobarating and sharing their work, they were able to assemble a large collection of data and examine clusters of gene variants and how they linked to blood pressure measurements taken from participants.

The first stage of the collaboration was a meta-analysis that pooled and re-analyzed the results from 17 genome-wide associations studies. The analysis involved looking at more than 2.5 million sections of DNA in more than 34,000 Europeans or people of European descent.

The researchers found variants in 12 chromosomal regions (areas on the DNA map) were consistently linked to high blood pressure readings, suggesting these were genes that controlled or were involved in the regulation of blood pressure.

The researchers then did two more meta-analyses, one that used DNA data on more than 71,000 people of European descent, and another that used DNA data from 12,300 people of Indian Asian descent.

Amassing the results from all three analyses together meant there was enough statistical power to show that 8 genetic regions of DNA were linked to systolic and diastolic blood pressure and with the risk of hypertension.

One of the regions contains genes for proteins that relax blood vessels and control how the kidneys get rid of sodium (these proteins are called natriuretic peptides). Newton-Cheh and his team had already found earlier this year that variations in these proteins affect blood pressure.

Another region that they found is known to be linked to a rare genetic condition that causes high blood pressure.

But the other 6 regions had not been linked with blood pressure before, said the researchers.

Newton-Cheh said:

"These findings suggest exciting new avenues for blood pressure treatments that have not been explored because we had no way of knowing the gene regions were involved in blood pressure regulation."

Newton-Cheh said the next thing they intend to do is find which of the genes actually cause high blood pressure and how, so that one day therapies can use this knowledge to change their effect so as to treat, and maybe even prevent, hypertension.

"Genome-wide association study of blood pressure and hypertension."

Daniel Levy, Georg B Ehret, Kenneth Rice, Germaine C Verwoert, Lenore J Launer, Abbas Dehghan, Nicole L Glazer, Alanna C Morrison, Andrew D Johnson, Thor Aspelund, Yurii Aulchenko, Thomas Lumley, Anna Köttgen, Ramachandran S Vasan, Fernando Rivadeneira, Gudny Eiriksdottir, Xiuqing Guo, Dan E Arking, Gary F Mitchell, Francesco U S Mattace-Raso, Albert V Smith, Kent Taylor, Robert B Scharpf, Shih-Jen Hwang, Eric J G Sijbrands, Joshua Bis, Tamara B Harris, Santhi K Ganesh, Christopher J O'Donnell, Albert Hofman, Jerome I Rotter, Josef Coresh, Emelia J Benjamin, André G Uitterlinden, Gerardo Heiss, Caroline S Fox, Jacqueline C M Witteman, Eric Boerwinkle, Thomas J Wang, Vilmundur Gudnason, Martin G Larson, Aravinda Chakravarti, Bruce M Psaty & Cornelia M van Duijn.

Nature Genetics, Published online: 10 May 2009

doi:10.1038/ng.384

Sources: Massachusetts General Hospital.

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Section Issues On Medicine: Cardiology