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MUHC-led research identifies risk-factor genes for type 2 diabetes

A new study led by researchers at the McGill University Health Centre has identified four genes that increase the risk of developing type 2 diabetes. This form of diabetes is the most common worldwide and affects nearly 2 million Canadians. In recent years, the prevalence of Type 2 diabetes has increased rapidly. This genetic discovery may help stem this rise.

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Keywords: muhc-led, research, identifies, risk-factor, genes, type, diabetes, muhc, led, identify, risk, factor, gene, diabete

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1. 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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2. Research team identifies new Alzheimer's gene
   06-06-2007 · EurekAlert!
   A study comparing more genetic markers in the DNA of people with and without Alzheimer's disease than ever before enabled researchers to identify a common gene that appears to increase one's risk for developing Alzheimer's disease. The finding by researchers at the Translational Genomics Research Institute, Banner Alzheimer's Institute, Kronos Science Laboratory and their collaborative partners, suggests that the gene -- called GAB2 -- modifies an individual's risk when associated with other genes, including APOE4.
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3. New Joslin research identifies sirtuin protein instrumental in fat production and metabolism
   08-15-2007 · EurekAlert!
   A new Joslin Diabetes Center-led study has identified a protein found in fat cells that may play a major role in how fat is produced and stored, offering a new target for treatments to prevent obesity and reduce the risk for type 2 diabetes. This latest research appears in the August 2007 issue of Cell Metabolism.
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4. Discovery suggests location of genes for breast density, a strong risk factor for breast cancer
   08-31-2007 · EurekAlert!
   Studying the DNA of 889 people, gene hunters at the Mayo Clinic and H. Lee Moffitt Cancer Centers have identified a region on chromosome 5p that is significantly associated with dense breast tissue, a known risk factor for breast cancer. The findings are published in the September 1 issue of Cancer Research, a publication of the American Association for Cancer Research.
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5. U-M, Israeli scientists report major advance in search for genes associated with colon cancer
   07-08-2007 · EurekAlert!
   An international team of researchers is reporting on a 10-year study of colon cancer among Israeli Jews and Arabs. The researchers, led by a team from the University of Michigan Comprehensive Cancer Center, discovered a genetic marker that increased a person's risk of colon cancer by 23 percent. At the same time, three other research teams are reporting similar findings involving the same gene, strengthening the likelihood that this particular marker plays a role in colon cancer.
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6. Research aims to identify markers for menopausal women at risk for deadly blood clot
   08-08-2007 · EurekAlert!
   In women, hormone therapy is a risk factor for venous thrombosis, a blood clot forming deep inside the vein. Although the disorder is rare, it increases exponentially during menopause and can be deadly. Hormone trials conducted thus far, focusing on proteins in blood coagulation, have not yet led to a risk profile, precluding identification of women at risk. Mayo Clinic researchers have now developed a novel concept that uses blood platelets to define thrombotic risk.
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7. Breakthrough in understanding type-2 diabetes as key genes identified
   02-14-2007 · EurekAlert!
   The most important genes associated with a risk of developing type-2 diabetes have been identified, scientists report today in a new study. The research, published online in Nature, is the first time the genetic makeup of any disease has been mapped in such detail. It should enable scientists to develop a genetic test to show an individual their likelihood of developing diabetes mellitus type 2, commonly known as type-2 diabetes.
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8. A tumor marker Ca 19-9 in diabetics can lead to misdiagnosis of pancreatic cancer
   10-13-2007 · EurekAlert!
   Type 2 diabetes mellitus is a risk factor for pancreatic cancer which is increasing worldwide. A research group from Turkey has found that the use of a tumor marker, Ca 19-9, in diabetics with a standard reference value can lead to misdiagnosis of pancreatic cancer.
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9. Research team identifies additional genetic risk factors for Crohn's disease
   04-15-2007 · EurekAlert!
   An international research team has identified several novel genetic variations associated with the risk of Crohn's disease. One of the identified genes establishes a role for autophagy, a previously unsuspected biological pathway, in Crohn's disease pathology, and the report documents functional studies which establish that this gene is integral to immune responses to intestinal bacteria.
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10. Researchers identify a role for glucose-sensing neurons in type 2 diabetes
    08-29-2007 · EurekAlert!
    In cases of Type 2 diabetes, the body's cells fail to appropriately regulate blood glucose levels. Research led by scientists at Beth Israel Deaconess Medical Center and Oregon Health & Science University describes a previously unrecognized role for glucose-sensing neurons in the onset of the disease demonstrating that an important component of Type 2 diabetes may indeed be "in your head."
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