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Twin studies reveal genetic components leading to cardiac and kidney disease

04-17-2007 · EurekAlert!

Daniel O'Connor, M.D., Professor of Medicine and Pharmacology at the University of California, San Diego (UCSD) School of Medicine has studied about 265 twin pairs over the past few years, which has led him to some surprising discoveries.

Keywords: twin, studies, reveal, genetic, components, leading, cardiac, kidney, disease, study, component

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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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Genetic breakthrough offers promise in tackling kidney tumors
01-10-2008 · EurekAlert!
Early tests show promising results for a new treatment for tuberous sclerosis, which can cause tumors in organs throughout the body. The UK study is led by Cardiff University's Institute of Medical Genetics, which was the first to identify the genes linked to the disease.
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Combination therapy stops loss of kidney function in rare genetic disease
07-25-2007 · EurekAlert!
A combination of two types of blood pressure-lowering drugs -- an angiotensin-converting enzyme inhibitor (ACEI) plus an angiotensin-receptor blocker (ARB), added to enzyme replacement therapy (ERT) with agalsidase-beta (Fabrazyme, Genzyme Corporation, Cambridge, Mass.) -- is the first treatment shown to stop progressive loss of kidney function in patients with severe kidney involvement due to the rare genetic disorder Fabry disease, reports a study in the September Journal of the American Society of Nephrology.
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Breakdown of kidney's ability to clean its own filters likely causes disease
01-29-2008 · EurekAlert!
The kidney actively cleans its most selective filter to keep it from clogging with blood proteins, scientists from Washington University School of Medicine in St. Louis reveal in a new study. Researchers showed that breakdown of this self-cleaning feature can make kidneys more vulnerable to dysfunction and disease.
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Chronic pain should be considered a disease
02-15-2008 · EurekAlert!
The concept that chronic pain is a disease in its own right is leading to new specific treatments aimed at physical, psychological, and environmental components of this major disease, including genetic predisposition, according to a world renowned pain medicine expert.
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Genetic marker linked to aggressive prostate cancer
05-20-2007 · EurekAlert!
Northwestern University researchers have discovered that a recently identified genetic marker for prostate cancer is linked to a highly aggressive form of the disease. These findings ultimately will aid the development of a simple blood test to predict who is susceptible to this aggressive cancer. Knowing which patients carry this genetic marker also will guide doctors in how they treat the cancer. The study showed a strong hereditary component to this aggressive cancer.
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Mayo Clinic study finds heart transplant patients benefit from new approach to immunosuppression
04-26-2007 · EurekAlert!
A new immunosuppression regimen for heart transplant patients can improve kidney function and prevent transplant coronary artery disease, according to two new Mayo Clinic studies. Mayo researchers will report their findings on April 26 at the International Society for Heart & Lung Transplantation Annual Meeting and Scientific Session in San Francisco.
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Researchers reveal genetic secrets of devastating human parasite
09-20-2007 · EurekAlert!
An international team of researchers has revealed the genetic secrets of one of the world's most debilitating human parasites, Brugia malayi, which the World Health Organization estimates has seriously incapacitated and disfigured more than 40 million people around the globe. The study reveals dozens of potential new targets for drugs or vaccines and should provide new opportunities for understanding, treating and preventing elephantiasis, the disfiguring disease caused by the Brugia malayi parasite.
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A unique twin study on the increased cardiometabolic risk in obesity
02-13-2007 · EurekAlert!
A unique monozygotic twin study by Finnish researchers found that obesity, already in its early stages and independent of genetic influences, is associated with deleterious alterations in the lipid metabolism known to facilitate atherogenesis, inflammation and insulin resistance. By studying monozygotic twins discordant for obesity the research group was able to eliminate effects caused by genetic differences related to obesity and reveal effects attributable to environmental and life-style differences.
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Largest ever study of genetics of common diseases published today
06-06-2007 · EurekAlert!
The Wellcome Trust Case Control Consortium, the largest ever study of the genetics behind common diseases such as diabetes, rheumatoid arthritis and coronary heart disease, today publishes its results in the journals Nature and Nature Genetics. The study examined DNA samples from 17,000 people across the UK, bringing together 50 leading research groups and 200 scientists in the field of human genetics. Over two years, they analysed almost 10 billion pieces of genetic information.
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