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Study finds gender differences in renal and other genes contributing to blood pressure

08-08-2007 · EurekAlert!

In a new study, researchers examined the differential contribution of genetic factors involved in regulating blood pressure based on samples drawn from a large community. They found significant differences in genetic contributors to blood pressure in males vs. females.

Keywords: study, gender, differences, renal, genes, contributing, blood, pressure, difference, 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 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.
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Cause of gender differences in blood pressure, kidney damage under study
05-02-2007 · EurekAlert!
While men and women both get high blood pressure and related kidney disease, the path to get there is shorter, steeper and just different for men, researchers say.
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Study finds differences between blood pressure medicines and newly-diagnosed diabetes
01-19-2007 · EurekAlert!
Researchers at Rush University Medical Center analyzed the data from 22 randomized clinical trials, and have found significant differences between antihypertensive drugs. ACE-inhibitors and the newer angiotensin receptor blockers, or ARBs prevent people from getting diabetes, and the older diuretics or beta-blockers, increase the chance that a person becomes diabetic, compared to either placebo (inactive sugar-pills) or calcium channel blockers according to a study published in the January 20, 2007 issue of the Lancet.
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Study finds gender differences related to eating and body image
12-14-2006 · EurekAlert!
Researchers have discovered a subtle new difference between men and women -- this one occurring in the realm of eating.
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Pulse pressure identified as important risk factor for atrial fibrillation
02-20-2007 · EurekAlert!
Increased pulse pressure (the difference between systolic and diastolic blood pressure) appears to be an important predictor of the risk for new onset atrial fibrillation, according to a study in the February 21 issue of JAMA.
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Genes and drugs team up to lower blood pressure
09-12-2007 · EurekAlert!
Patients with high blood pressure respond very differently to anti-hypertensive medication, making treatment selection tricky for physicians. But new research published in the online open access journal, BMC Medical Genetics, pinpoints a number of gene-drug interactions that could allow medication to be tailored to individual patients based on their genetics.
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Gene variations associated with effectiveness of blood pressure medications
01-22-2008 · EurekAlert!
Patients with hypertension and certain gene variations experienced varying results with some blood pressure medications, suggesting matching a patient's genotype with certain hypertension medications could result in more favorable outcomes, according to a study in the Jan. 23 issue of JAMA.
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Large VA study finds seasonal differences in blood pressure
11-05-2007 · EurekAlert!
Fewer people treated for high blood pressure return to normal pressure levels in the winter compared to those treated in the summer, Veterans Affairs researchers reported at the American Heart Association's Scientific Sessions 2007.
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Study identifies steps to improve safety of renal artery stenting
03-26-2007 · EurekAlert!
High blood pressure is the most common chronic medical condition in the US, and the most common identifiable cause is renal artery stenosis. Renal artery stenting is a widely performed but controversial procedure for patients. Use of a platelet inhibitor may make renal artery stenting safer for patients, especially when used in combination with an embolic protection device, according to a study presented today at the American College of Cardiology's Innovation in Intervention: i2 Summit.
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