 |
|
Johns Hopkins scientists out a gene for gout
June 19, 2009Having partnered last year with an international team that surveyed the genomes of 12,000 individuals to find a genetic cause for gout, Johns Hopkins scientists now have shown that the malfunctioning gene they helped uncover can lead to high concentrations of blood urate that forms crystals in joint tissue, causing inflammation and pain - the hallmark of this disease.
The ABCG2 gene, they found, makes a protein that normally transports urate out of the kidney and into urine before the waste product does any harm. In studies using frog egg cells genetically engineered with human DNA, the Hopkins researchers established the role of the ABCG2 gene as a cause of gout, lending credence to suspicions that metabolic deficiencies, in addition to too much rich food and alcohol, are mostly to blame for this painful type of arthritis that affects 3 million Americans. The gene, they believe, may be responsible for some 10 percent of gout in Caucasians.
A report on the research, funded by the National Institutes of Health, was published June 8 in the online Early Edition PNAS.
The research began with a "genome-wide association study" that involved participants of the Artherosclerosis Risk in Communities Study, originally initiated two decades ago to examine the roots of heart disease. Over the course of that research, blood was collected from the study participants and analyzed for a variety of chemical elements, including uric acid. Subjects also reported whether they had ever been diagnosed with gout, enabling researchers to link information from DNA, uric acid levels and gout.
By analyzing associations between blood uric acid levels and genotypes, the researchers identified the gene known as ABCG2 and specifically a certain mutation as a candidate for causing the joint inflammation and pain that are symptoms of gout. Because animal models for gout are not representative of humans - all mammals except for higher primates have an enzyme that efficiently breaks down uric acid - the researchers turned to genetic engineering to figure out just how the human ABCG2 gene might work to regulate uric acid levels, and how its mutation may lead to gout.
First, the team injected both normal and the mutant versions of the human ABCG2 gene into frog eggs which served as the live "factories" for producing the protein made by the gene. A couple of days later, after the egg cells produced lots of ABCG2 protein, the researchers bathed them in a radioactive-tagged uric acid bath.
Using the tag to identify and measure how much urate accumulated in the cells, the investigators then measured how quickly the urate left the cell. Comparing these so-called "efflux rates" to rates in control cells injected with the normal ABCG2, the scientists found that the cells with the mutant ABCG2 protein excreted uric acid at a rate just half of normal.
"We were able to show for what we believe is the first time that the ABCG2 protein is vital for transporting urate out of cells,"says Owen Woodward, Ph.D., a postdoctoral fellow in physiology in the Johns Hopkins University School of Medicine.
The researchers further showed that the ABCG2 protein is located in the kidney at a location where urate exretion takes place. They suggest that a lack of efficiency in removing urate from the blood leads to its increased concentration and crystallization. In humans, these crystals get caught in joint tissues, leading to painful inflammation.
"As the first major gene identified to cause gout, we believe that ABCG2 also represents an attractive new drug target," says Michael Kottgen, M.D., a biological chemistry research associate in the Johns Hopkins University School of Medicine.
One strategy is to identify a drug that makes excretion faster and more efficient by activating the "urate transporter" protein.
"Instead of trying to limit urate production - the major current approach to gout treatment - newer treatments could focus on getting urate out of the bloodstream," Kottgen says. "We anticipate that activation of ABCG2 with a drug may help to promote excretion of urate."
"It's exciting that a finding from genome-wide association studies has been directly translated into better understanding physiology and perhaps will help us find better clinical therapies", says Anna Kottgen, M.D., M.P.H., an epidemiologist in the Johns Hopkins University Bloomberg School of Public Health.
Johns Hopkins Medical Institutions
The research began with a "genome-wide association study" that involved participants of the Artherosclerosis Risk in Communities Study, originally initiated two decades ago to examine the roots of heart disease. Over the course of that research, blood was collected from the study participants and analyzed for a variety of chemical elements, including uric acid. Subjects also reported whether they had ever been diagnosed with gout, enabling researchers to link information from DNA, uric acid levels and gout.
By analyzing associations between blood uric acid levels and genotypes, the researchers identified the gene known as ABCG2 and specifically a certain mutation as a candidate for causing the joint inflammation and pain that are symptoms of gout. Because animal models for gout are not representative of humans - all mammals except for higher primates have an enzyme that efficiently breaks down uric acid - the researchers turned to genetic engineering to figure out just how the human ABCG2 gene might work to regulate uric acid levels, and how its mutation may lead to gout.
First, the team injected both normal and the mutant versions of the human ABCG2 gene into frog eggs which served as the live "factories" for producing the protein made by the gene. A couple of days later, after the egg cells produced lots of ABCG2 protein, the researchers bathed them in a radioactive-tagged uric acid bath.
Using the tag to identify and measure how much urate accumulated in the cells, the investigators then measured how quickly the urate left the cell. Comparing these so-called "efflux rates" to rates in control cells injected with the normal ABCG2, the scientists found that the cells with the mutant ABCG2 protein excreted uric acid at a rate just half of normal.
"We were able to show for what we believe is the first time that the ABCG2 protein is vital for transporting urate out of cells,"says Owen Woodward, Ph.D., a postdoctoral fellow in physiology in the Johns Hopkins University School of Medicine.
The researchers further showed that the ABCG2 protein is located in the kidney at a location where urate exretion takes place. They suggest that a lack of efficiency in removing urate from the blood leads to its increased concentration and crystallization. In humans, these crystals get caught in joint tissues, leading to painful inflammation.
"As the first major gene identified to cause gout, we believe that ABCG2 also represents an attractive new drug target," says Michael Kottgen, M.D., a biological chemistry research associate in the Johns Hopkins University School of Medicine.
One strategy is to identify a drug that makes excretion faster and more efficient by activating the "urate transporter" protein.
"Instead of trying to limit urate production - the major current approach to gout treatment - newer treatments could focus on getting urate out of the bloodstream," Kottgen says. "We anticipate that activation of ABCG2 with a drug may help to promote excretion of urate."
"It's exciting that a finding from genome-wide association studies has been directly translated into better understanding physiology and perhaps will help us find better clinical therapies", says Anna Kottgen, M.D., M.P.H., an epidemiologist in the Johns Hopkins University Bloomberg School of Public Health.
Johns Hopkins Medical Institutions
Gout Current Events and Gout News RSSStudy supports possible role of urate in slowing Parkinson's disease progression
By examining data from a 20-year-old clinical trial, a research team based at the MassGeneral Institute for Neurodegenerative Diseases (MGH-MIND) and Harvard School of Public Health (HSPH), has found evidence supporting the findings of their 2008 study - that elevated levels of the antioxidant urate may slow the progression of Parkinson's disease.
Investment in Parkinson's disease data bank yields potential therapy
Individuals with Parkinson's disease who have higher levels of a metabolite called urate in their blood and in cerebrospinal fluid (CSF) have a slower rate of disease progression.
Rochester-led Parkinson's study pays off again, 2 decades later
Parkinson disease progresses more slowly in patients who have higher levels of urate, a chemical that at very high level is associated with gout, scientists have found.
Mutation in renin gene linked to inherited kidney disease
A mutation in a gene that helps regulate high blood pressure is a cause of inherited kidney disease, according to a new study by researchers at Wake Forest University School of Medicine, Charles University in Prague and colleagues.
Research identifies new link between tart cherries and risk factors for heart disease
New research continues to link tart cherries, one of today's hottest "Super Fruits," to lowering risk factors for heart disease.
Researchers discover that SLC2A9 is a high-capacity urate transporter in humans
An international team of researchers led by Professors Mark Caulfield and Patricia Munroe, from the William Harvey Research Institute at Barts and The London School of Medicine and Dentistry with Chris Cheeseman at the University of Alberta in Canada and Kelle Moley at the University of Washington in USA, have shown that the SLC2A9 gene, which encodes a glucose transporter, is also a high-capacity urate transporter, and thus possibly a new drug target for gout.
High levels of uric acid may be associated with high blood pressure
Reducing levels of uric acid in blood lowered blood pressure to normal in most teens in a study designed to investigate a possible link between blood pressure and the chemical, a waste product of the body's normal metabolism.
Blood urate levels associated with the progression of Parkinson's disease
Higher blood levels of the compound urate, a salt derived from uric acid that is associated with gout, may be associated with a slower progression of Parkinson's disease.
Researchers shed light on genetic factors behind UK's biggest killer
Researchers investigating the biochemical characteristics behind several everyday diseases have discovered a new chromosomal region to be strongly associated with the bad cholesterol, low density lipoprotein, (LDL).
Cherries may help reduce metabolic syndrome and heart disease risk factors
Increasing intake of antioxidant-rich cherries may help lower the risk of metabolic syndrome and cardiovascular disease, suggests a new study(1) presented today at the Experimental Biology annual meeting.
More Gout Current Events and Gout News Articles
 |
Beating Gout: A Sufferer's Guide to Living Pain Free by Victor Konshin (Author) Beating Gout is the most comprehensive and up-to-date book designed for the gout sufferer. Recent research has shown that up to 78% of doctors do not treat gout properly. This book sets the record straight on the best and most effective ways to treat gout attacks and manage gout's underlying condition, hyperuricemia. Beating Gout covers all aspects of the disease from its progression, diagnosis, treatment, to the latest research on diet and lifestyle choices that affect gout. Over five hundred research articles and texts were reviewed for this book. No other source has more practical, scientifically backed information that gout sufferers can start using immediately to reduce or stop gout attacks while living a healthier and pain free life. What you will learn: |
 |
Goutrin -Uric Acid Neutralizer for Gout (120 Capsules) Brand: Organika by Organika Uses: Gout, Arthritis, Sore joints. |
 |
Gout Hater's Cookbook I by Jodi Schneiter (Author) Gout Hater's Cookbook I, Recipes Lower in Purines and Lower in Fat. This cookbook features comprehensive lists of foods lower, relatively high and highest in purines. Designed specifically for persons suffering from gout. Includes recent research information concerning how different aspects of the diet (high purine vegetables, meat, seafood and dairy intake) affect the risk of gout. Consisting of 104 pages and over 90 recipes, this book offers a wide variety in cuisine. Sections contain: Appetizers, Beverages, Main Dishes, Sides, Sauces and Desserts. "Quick Snack" and "Small Change, Big Difference" boxes are scattered throughout. Fourth Edition, Revised, July, 2004. |
|
|
Goutrin -Uric Acid Neutralizer for Gout (60 Capsules) Brand: Organika by Organika Uses: Gout, Arthritis, Sore joints. |
 |
Getting Rid of Gout by Bryan Emmerson (Author) Anyone suffering from this traumatic arthritic condition will fully appreciate the new edition of Getting Rid of Gout. Included in the new sections are updated dietary guidelines, including current research on the role of diet in preventing gout, and a description of the new medications available for its treatment. Bryan Emmerson, a recognised authority on gout, argues that if control of the elevated concentrations of uric acid can be achieved through either diet or medication modifications, gout attacks will cease and there will be no further complications. He goes on to outline how effective prevention of gout requires sufferers to understand their condition, one that can be a result of both genetic and lifestyle factors. Written in an understandable and sympathetic manner with the... |
 |
The Ultimate Gout Formula by NutraBest, LLC The Ultimate Gout Formula is a proprietary herbal blend that contains phytonutrients that contribute to the support of the liver. It is in the liver where the protein break-down products that cause gout, purines and uric acid, tend to accumulate to harmful levels. The Ultimate Gout Formula aids in the processing of those compounds by providing the liver with all of the needed nutrients required to eliminate the harmful build up of uric acid. Gout is caused when there is over production of uric acid in normal purine metabolism in the body. High blood levels of uric acid in turn causes sodium monourate crystals to collect in the joint fluid and joint coverings leading to gout, a painful stiff swollen joint. Through the use of certain kinds of medications, a proper diet and exercise, gout... |
 |
Gout Hater's Cookbook II: The Low Purine Diet Cookbook by Jodi Schneiter (Author) The perfect addition to the Gout Hater's Collection, designed specifically for persons suffering from gout. This new book complies with the modified purine diet in its predecessor, Gout Hater's Cookbook. It also meets the requirements of the restricted purine diet. The recipes you will find in Book II feature a more detailed, albeit restriced, food list, for a delicious ovo-lacto- (eggs and milk allowed) vegetarian diet. Gout Hater's Cookbook II was put together in an effort to demonstrate just how delectably well you can eat, even on a restricted purine diet, while continually helping to lower your uric acid levels. Over 100 recipes, 112 pages, features comprehensive food lists of foods allowed and not allowed. Sections include Questions and Answers, Helpful... |
 |
Gout by Dr. Roy Porter (Author), G. S. Rousseau (Author), Roy Porter G.S. Rousseau (Author) Gout has interested medical writers and cultural commentators from the time of Ancient Greece. Historically seen as a disease afflicting upper-class males of superior wit, genius and creativity, it has included among its sufferers Erasmus, the Medici, Edward Gibbon, Samuel Johnson, Immanuel Kant and Robert Browning. Gout has also been the subject of medical folklore, viewed as a disease that protects its sufferers and assure long life. This book investigates the history of gout and through it offers a perspective on medical and social history, sex, prejudice and class and explains why gout was gender specific. The authors investigate medical thinking about gout through the ages, from Hippocrates and Galen through Paracelsus and Harvey to Archibald Garrod in the Victorian era and beyond.... |
 |
Carol Bond's Go Out Plex Caps 60's (A Natural Formulation of Celery Seed Extract, Black Cherry Fruit Extract, Turmeric Root, and Potassium to Control Gout Symptoms) by CAROL BOND HEALTH FOODS GOUT PLEX is a formulation to control gout symptoms. GOUT PLEX contains: Celery Seed Extract --- is a diuretic, has properties that reduce muscle spasms, calm the nerves and reduce inflammation. Black Cherry Fruit Extract --- has anthocyanins which relieve inflammation and pain. Turmeric Root --- anti-inflammatory Bromelain --- It has been credited with a number of health benefits including aiding digestion, speeding wound healing, and reducing inflammation. Potassium --- a diuretic; water balance and distribution, acid-base balance , muscle and nerve cell function, heart function, kidney and adrenal function.. |
 |
Gout Hater's Cookbook IV by Jodi Schneiter (Author) Gout Hater's fans will love to see this wonderful, delicious addition to the collection! Complete with information on the latest research results, Gout Hater's Cookbook IV provides a master index of all four volumes, as well as a wide variety of vegetarian and meat dishes. Special attention is also paid to apple cider vinegar, which assists in balancing the pH levels in the body. As with all books in the Gout Hater's Cookbook collection, each book can be purchased separately and independently of the others, with a minimal amount of recipe duplications (e.g., homemade margarine). With more than 100 tasty new recipes, Gout Hater's Cookbook IV serves as a welcome 10th anniversary celebration of the Gout Hater's Cookbook beginnings, as well as a reminder that diet limitations do not need... |
| © 2009 BrightSurf.com |