Navigation Links
International study identifies new gene targets for hypertension treatment

A new report from scientists at Massachusetts General Hospital (MGH) and their colleagues in centers around the world finds that common variants in 28 regions of DNA are associated with blood pressure in human patients. Of the identified regions, most were completely unsuspected, although some harbor genes suspected of influencing blood pressure based on animal studies. In the study receiving advance online publication in Nature, members of the International Consortium for Blood Pressure Genome-Wide Association Studies (ICBP-GWAS) analyzed genetic data from over 275,000 individuals from around the world. They also identified for the first time the involvement of an important physiologic pathway in blood pressure control, potentially leading to a totally new class of hypertension drugs.

"Identifying these novel pathways expands our current understanding of the determinants of blood pressure and highlights potential targets for new drugs to treat and prevent cardiovascular complications," says Christopher Newton-Cheh, MD, MPH, of the MGH Center for Human Genetic Research and the Cardiovascular Research Center, co-chair of the ICBP-GWAS Steering Committee and a senior and corresponding author on the Nature paper.

It is well known that hypertension can run in families and that some rare genetic syndromes raise blood pressure, but identifying genes associated with the common form of hypertension has been challenging. To get a study sample large enough to detect variants with modest effects, ICBP-GWAS researchers conducted a meta-analysis of 30 genome-wide association studies that included measurements of participants' blood pressures. Analysis of 2.5 million DNA sequence variants in more than 69,000 individuals of European ancestry identified several chromosomal regions where genes influencing blood pressure appeared to be located. To confirm the results of the first-stage analysis, the researchers genotyped the strongest variants in more than 133,000 additional individuals of European descent. Combining the results identified 28 gene regions associated with both systolic and diastolic blood pressure, of which 16 were novel. A second paper from the consortium also receiving online publication today in Nature Genetics, identified six additional novel variants..

Some of the new variants were already known to cause other diseases. "We were quite astonished to see that two common variants known for decades to cause hemochromatosis an iron overload condition that affects as many as 1 in 300 Americans were also associated with higher blood pressure," says Newton-Cheh. "The hemochromatosis genes are part of a physiologic pathway that is also involved in pulmonary hypertension, but this finding opens our eyes to its potential involvement in systemic hypertension."

To test whether the blood pressure variants identified in Europeans were associated with blood pressure in other ethnicities, the consortium genotyped almost 74,000 individuals of either East Asian, South Asian or African ancestries. Genetic risk scores incorporating all identified variants were strongly associated with blood pressure levels in each of those groups and also with the risk of stroke and coronary heart disease. "Seeing that the blood pressure variants in aggregate lead to stroke and heart attack was perhaps not surprising, given the evidence that blood pressure treatment lowers these risks," said Newton-Cheh.

But the most important finding may be identification of a new pathway central to blood pressure regulation. Three of the 28 blood-pressure-associated regions include genes that are part of a pathway called the cyclic guanosine monophosphate (cGMP) system, which is involved in the relaxation of blood vessels and excretion of sodium by the kidneys, two fundamental mechanisms of hypertension treatment. Animal studies have suggested a role for this pathway in blood pressure control, and the current findings strongly support its relevance in human patients.

"We have previously shown that variants in natriuretic peptide genes, part of the cGMP system, influence blood pressure. We were therefore pleased but not surprised to see other genes that influence the cGMP system in this recent crop of discoveries," said Newton-Cheh, an assistant professor of Medicine at Harvard Medical School. "The greatest attention in blood pressure research has been focused on another pathway called the renin-angiotensin-aldosterone system (RAAS), which is targeted by several hypertension therapies. But only one common gene variant has been associated with genes in the RAAS pathway.

"Finding several independent associations that converge on cGMP points to its central importance in blood pressure control," he adds. "In fact, there are several drugs that target these systems in development to treat pulmonary hypertension and heart failure, but our findings suggest that they could have a much larger role in hypertension treatment in general. The next phase of our research will focus on finding additional genes and variants that influence blood pressure and on establishing how some of the cGMP-involved genes affect blood pressure in humans and respond to existing drugs and to those in development."


Contact: Kristen Stanton
Massachusetts General Hospital

Related biology news :

1. Media invited: AVS 58th International Symposium and Exhibition
2. Mapping a model: International research on plant species appears in journal Nature
3. Systech International and Zetes Partner to Meet Europes Emerging Pharmaceutical Regulatory Requirements
4. Thermophile experts to hold international meeting Sept. 11-16 near Yellowstone National Park
5. International pharmacogenomics conference to focus on better drug treatment based on genetics
6. American Society of Human Genetics to host 12th International Congress of Human Genetics
7. Visiting researcher at IU leads international team in formal identification of new fungi class
8. Vanderbilt researchers, international team, uncover genes linked to multiple sclerosis
9. Worlds largest sheep an international traveler
10. NYU Langone Medical Centers tip sheet to the 2011 Alzheimers Association International Conference
11. 19th Conference of the International Society for Sexually Transmitted Disease Research
Post Your Comments:
(Date:5/9/2016)... , UAE, May 9, 2016 ... it comes to expanding freedom for high net worth ... Even in today,s globally connected world, there is still ... system could ever duplicate sealing your deal with a ... second passports by taking advantage of citizenship via investment ...
(Date:4/28/2016)... , April 28, 2016 First quarter 2016: ... up 966% compared with the first quarter of 2015 ... SEK 589.1 M (loss: 18.8) and the operating margin was 40% ... 0.32) Cash flow from operations was SEK 249.9 M ... revenue guidance is unchanged, SEK 7,000-8,500 M. The operating ...
(Date:4/19/2016)... , UAE, April 20, 2016 ... implemented as a compact web-based "all-in-one" system solution for ... biometric fingerprint reader or the door interface with integration ... modern access control systems. The minimal dimensions of the ... readers into the building installations offer considerable freedom of ...
Breaking Biology News(10 mins):
(Date:6/24/2016)... ... June 24, 2016 , ... While the majority of commercial spectrophotometers and ... and the 6000i models are higher end machines that use the more unconventional z-dimension ... light beam from the bottom of the cuvette holder. , FireflySci has developed ...
(Date:6/23/2016)... , ... June 23, 2016 , ... ... release of its second eBook, “Clinical Trials Patient Recruitment and Retention Tips.” Partnering ... retention in this eBook by providing practical tips, tools, and strategies for clinical ...
(Date:6/23/2016)...   Boston Biomedical , an industry leader ... target cancer stemness pathways, announced that its lead ... Designation from the U.S. Food and Drug Administration ... gastroesophageal junction (GEJ) cancer. Napabucasin is an orally ... stemness pathways by targeting STAT3, and is currently ...
(Date:6/23/2016)... 23, 2016 A person commits a crime, and ... to track the criminal down. An outbreak of ... Drug Administration (FDA) uses DNA evidence to track down the ... Sound far-fetched? It,s not. The FDA has increasingly used a ... of foodborne illnesses. Put as simply as possible, whole genome ...
Breaking Biology Technology: