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Researchers show surprising interaction between genes, gender and hypertension

12-15-2006 · EurekAlert!

In surprising results, a study of more than 1,200 patients with extremely low or high blood pressure by researchers at the University of California, San Diego School of Medicine showed that the influence of genes on blood pressure may vary based on gender.

Keywords: researchers, show, surprising, interaction, genes, gender, hypertension, researcher, gene

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Advance in understanding of blood pressure gene could lead to new treatments
02-04-2007 · EurekAlert!
Research by scientists at UCL (University College London) has clearly demonstrated for the first time the structure and function of a gene crucial to the regulation of blood pressure. The discovery could be important in the search for new treatments for illnesses such as heart disease, the UK's biggest killer. In a paper published online today in Nature Medicine, the team, led by Professor Patrick Vallance and Dr James Leiper, UCL Department of Medicine, reveal the role of the human gene dimethylarginine dimethylaminohydrolase (DDAH), showing that loss of DDAH activity disrupts nitric oxide (NO) production. NO is critical in the regulation of blood pressure, nervous system functions and the immune system. The role of DDAH is to break down modified amino acids (Asymmetric dimethylarginine (ADMA) and monomethyl arginine (L-NMMA)) that are produced by the body and have been shown to inhibit NO synthase. These molecules accumulate in various disease states including diabetes, renal failure and pulmonary and systemic hypertension, and their concentration in plasma (the fluid component of blood) is strongly predicative of cardiovascular disease and death. In a healthy human body, the majority of ADMA is eliminated through active metabolism by DDAH. Scientists have hypothesised that if DDAH function is impaired, NO production is reduced, and that this could be an important feature of increased cardiovascular risk. To examine this pathway in more detail, the researchers deleted the DDAH gene in mice. These mice went on to develop hypertension, or high blood pressure. They also designed specific inhibitors (small molecules) which bind to the active site of human DDAH. These small molecule inhibitors also induced hypertension in mice, confirming the importance of DDAH in the regulation of blood pressure. Dr Leiper, UCL Medicine, said: “These genetic and chemical approaches to disrupt DDAH showed remarkably consistent results, and provide compelling evidence that loss of DDAH function increases the concentration of ADMA and thereby disrupts vascular NO signalling. “There has been considerable scientific interest in this pathway and the role of ADMA as a novel risk factor, but so far there's been little evidence to support the idea that it's a cause of disease, rather than just a marker. Genes and their pathways are crucial to our understanding of cardiovascular disease and a better understanding of DDAH-1 could lead to important new treatments. “It could help us to establish if genetic variation predisposes certain people to these diseases, or whether environmental factors exert some of their effects through modulation of DDAH activity. “Our research also shows that this pathway could be harnessed therapeutically to limit production of NO in certain situations where too much nitric oxide is a bad thing; for example, hypotension and septic shock. These are some of the biggest problems in intensive care medicine and there is a huge unmet need for drug treatments.” The study, which was carried out at UCL's Rayne Institute, was funded by grants from the British Heart Foundation, the Wellcome Trust and the Medical Research Council. Professor Jeremy Pearson, Associate Medical Director of the British Heart Foundation, said: "The unexpected finding in the 1980s that a simple gas, nitric oxide (NO), is made by cells in the blood vessel wall and is a powerful control of blood vessel relaxation led to the award of the Nobel Prize in 1998 to its discoverers. "More recently, there has been increasing evidence that impairment of NO production is likely to be an important factor in the development of heart and circulatory disease, but the mechanisms responsible are not fully understood. "This study suggests for the first time that the loss of the activity of the enzyme DDAH-1 leads to reduced NO production and may cause heart and circulatory disease. These findings are likely to be important in the search for new ways to optimise the health of our blood vessels." ### Notes for Editors 1. For more information, please contact Ruth Metcalfe in the UCL Media Relations Office on tel: +44 (0)20 7679 9739, mobile: +44 (0)7990 675 947, out of hours: +44 (0)7917 271 364, e-mail: r.metcalfe@ucl.ac.uk2. 'Disruption of methylarginine metabolism impairs vascular homeostasis' is published in the February issue of the journal Nature Medicine. Advance online publication is embargoed to 18.00 GMT (13.00 US Eastern) Sunday 4 February 2007. Journalists can obtain copies of the paper by contacting the UCL Media Relations Office.3. The study was funded by the British Heart Foundation, the Wellcome Trust and the Medical Research Council. About UCL Founded in 1826, UCL was the first English university established after Oxford and Cambridge, the first to admit students regardless of race, class, religion or gender, and the first to provide systematic teaching of law, architecture and medicine. In the government's most recent Research Assessment Exercise, 59 UCL departments achieved top ratings of 5* and 5, indicating research quality of international excellence. UCL is the fourth-ranked UK university in the 2006 league table of the top 500 world universities produced by the Shanghai Jiao Tong University. UCL alumni include Mahatma Gandhi (Laws 1889, Indian political and spiritual leader); Jonathan Dimbleby (Philosophy 1969, writer and television presenter); Junichiro Koizumi (Economics 1969, Prime Minister of Japan); Lord Woolf (Laws 1954, Lord Chief Justice of England & Wales); Alexander Graham Bell (Phonetics 1860s, inventor of the telephone), and members of the band Coldplay.
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Researchers show that veins stiffen as we age
10-31-2006 · EurekAlert!
As if creaking joints and hardening of the arteries weren't bad enough, a research team from the University of Delaware and the Christiana Care Health System has now confirmed that even our veins stiffen as we age.And that physiological change may be an important factor in the development of high blood pressure, or hypertension, which currently affects an estimated 65 million Americans, most of them older adults, according to UD researcher William Farquhar.
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Reactivated gene shrinks tumors
01-24-2007 · EurekAlert!
Many cancers arise due to defects in genes that normally suppress tumor growth. Now, for the first time, MIT researchers have shown that re-activating one of those genes in mice can cause tumors to shrink or disappear.
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Autism Consortium releases data on genes involved in autism to researchers worldwide
10-22-2007 · EurekAlert!
The Autism Consortium, a group of researchers, clinicians and families dedicated to accelerating research and enhancing clinical care for autism, announced today that it has completed the first genome scan for Autism Spectrum Disorders through its Autism Gene Discovery Project and released the reference data set to a database that autism researchers around the world can use. The scan was conducted on genetic data from more than 3,000 children with ASD and their families.
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Several genes that regulate the disease SLE have been identified
01-22-2008 · EurekAlert!
Swedish researchers, in collaboration with foreign colleagues, have identified a number of new genes that can be tied to the disease SLE, including a gene that hopefully might be used to treat the disease in the future by regulating the production of antibodies. These unique findings are being published in three articles in the new issue of the journal Nature Genetics.
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Smell experience during critical period alters brain
12-05-2007 · EurekAlert!
Genes may provide the land, but experience defines the landscape. Now, researchers at Rockefeller University show that during the first few days of life, chronic exposure to carbon dioxide rather than air alters the activity of projection neurons and interneurons in the fly brain -- research that is first to show that the olfactory system is plastic.
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UGA researcher leads effort to sequence and catalog conifer genes for future biofuels research
08-17-2007 · EurekAlert!
Jeffrey Dean, professor of forest biotechnology in the University of Georgia Warnell School of Forestry and Natural Resources, is spearheading a project at the US Department of Energy's Joint Genome Institute that will greatly expand the gene catalog for pines and initiate the first gene discovery efforts in five other conifer families.
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Prenatal arsenic exposure can alter genes
11-22-2007 · Massachusetts Institute of Technology (MIT)
The children of mothers whose water supplies were contaminated with arsenic during their pregnancies harbored gene expression changes that may lead to cancer and other diseases later in life, MIT researchers reported in a new study.
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Lupus gene finding prompts call for more DNA samples
12-02-2007 · EurekAlert!
Wellcome Trust researchers have identified a key gene involved in the disease lupus, which affects around 50,000 people in the UK, mostly women. The lead researcher behind the study has called for more patients to volunteer DNA samples to enable them to further study the underlying causes of the disease.
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'Junk' DNA now looks like powerful regulator, Stanford researcher finds
04-23-2007 · EurekAlert!
Large swaths of garbled human DNA once dismissed as junk appear to contain some valuable sections, according to a new study by researchers at the Stanford University School of Medicine and the University of California-Santa Cruz. The scientists propose that this redeemed DNA plays a role in controlling when genes turn on and off.
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