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Study fails to verify gene variations as risk factors for certain cardiovascular problems

04-10-2007 · EurekAlert!

New research has failed to confirm findings from smaller studies that 85 gene variations are associated with an increased risk for acute coronary syndromes (ACS), which includes heart attack and a type of angina, according to a study in the April 11 issue of JAMA.

Keywords: study, fails, verify, gene, variations, risk, factors, certain, cardiovascular, problems, fail, variation, factor, problem

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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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HIV infection appears to increases the risk of heart attack
04-24-2007 · EurekAlert!
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Study reveals value of schizophrenia-related gene variation
02-13-2007 · EurekAlert!
University of Iowa researchers have learned more about a genetic variation that is a small risk factor for a mild form of schizophrenia yet also is associated with improved overall survival.
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Vitamin D, variations in its receptor and prostate cancer
03-19-2007 · EurekAlert!
Results of this study by Haojie Li and colleagues suggest that vitamin D deficiency is common among men in the US, and that vitamin D status and genetic variation in the VDR gene affect prostate cancer risk.
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Research linking Ashkenazi Jews & breast cancer genes beset by problems
11-01-2006 · EurekAlert!
Genetic research over the past decade has linked Ashkenazi Jewish ethnicity to an increased risk for hereditary breast cancer, so much so that certain gene mutations have become known as "Jewish ancestral mutations." But a new study released in the November 2006 issue of the American Journal of Public Health challenges this population-based approach, warning that disparities in access to care and other unintended consequences for specific ethic groups can result, and may have already occurred.
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Research linking Ashkenazi Jews and breast cancer genes beset by problems
11-01-2006 · EurekAlert!
Genetic research over the past decade has linked Ashkenazi Jewish ethnicity to an increased risk for hereditary breast cancer, so much so that certain gene mutations have become known as "Jewish ancestral mutations." But a new study released in the November 2006 issue of the American Journal of Public Health challenges this population-based approach, warning that disparities in access to care and other unintended consequences for specific ethic groups can result, and may have already occurred.
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Vitamin D, variations in its receptor, and prostate cancer
03-19-2007 · EurekAlert!
Results of this study by Haojie Li and colleagues suggest that vitamin D deficiency is common among men in the US, and that vitamin D status and genetic variation in the VDR gene affect prostate cancer risk.
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NHLBI media availability: Overweight girls at risk for cardiovascular disease
01-08-2007 · EurekAlert!
Results from the NHLBI Growth and Health Study of more than 2,300 girls suggest that girls as young as age 9 who are overweight are at increased risk for short-term and long-term problems that increase the chances of developing cardiovascular disease. Those who were overweight were more likely to have elevated blood pressure and cholesterol levels compared to girls who were not overweight. The study also provides insight into differences between African-American and Caucasian girls.
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GABRA2 genotype may moderate alcohol-psychotherapy outcomes
10-24-2007 · EurekAlert!
Previous studies have shown that the GABRA2 gene is related to the risk for alcohol dependence. New research goes one step further, looking at how variation in the GABRA2 gene may affect drinking behavior over time and how people respond to alcohol treatment. Variation in GABRA2 can modify overall drinking behavior, and may also have an impact on the success of certain types of psychotherapy used to treat alcohol dependence.
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Normal role for schizophrenia risk gene identified
09-07-2007 · EurekAlert!
How the gene that has been pegged as a major risk factor for schizophrenia and other mood disorders that affect millions of Americans contributes to these diseases remains unclear. However, the results of a new study by Hopkins researchers and their colleagues, appearing in Cell this week, provide a big clue by showing what this gene does in normal adult brains.
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