 |
|
Rare mutation causes early heart disease and metabolic syndrome
March 02, 2007New Haven, Conn.—Yale School of Medicine researchers have identified a rare defect in a single gene that poses a substantial risk for metabolic syndrome and early heart disease, the leading cause of death worldwide.
The international study, led by Arya Mani, M.D., assistant professor of cardiology, and Richard Lifton, M.D., chair of genetics at Yale, identifies a new pathway implicated in heart disease. Even though the genetic mutation is very rare, these findings point to new approaches for improving this aspect of health.
"These findings indicate that altered activity of a well-known signaling pathway, Wnt, has large effects on multiple metabolic pathways that contribute to cardiovascular disease," said Mani.
Coronary artery disease (CAD) is commonly caused by metabolic syndrome, which includes a constellation of risk factors such as high low-density lipoprotein (LDL) cholesterol, high triglycerides, low high-density lipoprotein (HDL) cholesterol, hypertension and diabetes.
This study was based on a large family of Iranian ancestry that had an extraordinary prevalence of early CAD. Among 58 blood relatives, 28 were diagnosed with early CAD at or before age 50 for the men, and 55 for the women. Twenty-three of the 28 died from CAD at young ages. In contrast, relatives without early CAD died at an average age of 81. The relatives with CAD had high LDL, high triglycerides, hypertension, and diabetes, while their unaffected relatives did not. The relatives with CAD also were predisposed to osteoporosis, which is particularly interesting given recent evidence of association of osteoporosis with CAD.
By comparing the inheritance of CAD to the inheritance of each chromosome segment in the pedigree, the team narrowed the location of the disease-causing gene to a short segment of chromosome 12. In this region, they found a single mutation in a gene called LRP6, which acts in the Wnt signaling pathway and which was previously known to be involved in development and in certain forms of cancer. The mutation changed one amino acid in the protein, which the team showed altered the activity of the protein encoded by LRP6.
"The reason for the observed association of multiple risk factors with one another has been a mystery," Lifton said.
"Our findings have implicated the Wnt signaling pathway in the development of many risk factors and early CAD. We expect that studies of the Wnt signaling pathway in patients with early CAD, and metabolic syndrome, will provide new insight into the basic biology of disease causation and allow new approaches to disease prevention."
Yale University
Coronary artery disease (CAD) is commonly caused by metabolic syndrome, which includes a constellation of risk factors such as high low-density lipoprotein (LDL) cholesterol, high triglycerides, low high-density lipoprotein (HDL) cholesterol, hypertension and diabetes.
This study was based on a large family of Iranian ancestry that had an extraordinary prevalence of early CAD. Among 58 blood relatives, 28 were diagnosed with early CAD at or before age 50 for the men, and 55 for the women. Twenty-three of the 28 died from CAD at young ages. In contrast, relatives without early CAD died at an average age of 81. The relatives with CAD had high LDL, high triglycerides, hypertension, and diabetes, while their unaffected relatives did not. The relatives with CAD also were predisposed to osteoporosis, which is particularly interesting given recent evidence of association of osteoporosis with CAD.
By comparing the inheritance of CAD to the inheritance of each chromosome segment in the pedigree, the team narrowed the location of the disease-causing gene to a short segment of chromosome 12. In this region, they found a single mutation in a gene called LRP6, which acts in the Wnt signaling pathway and which was previously known to be involved in development and in certain forms of cancer. The mutation changed one amino acid in the protein, which the team showed altered the activity of the protein encoded by LRP6.
"The reason for the observed association of multiple risk factors with one another has been a mystery," Lifton said.
"Our findings have implicated the Wnt signaling pathway in the development of many risk factors and early CAD. We expect that studies of the Wnt signaling pathway in patients with early CAD, and metabolic syndrome, will provide new insight into the basic biology of disease causation and allow new approaches to disease prevention."
Yale University
Metabolic Syndrome News and Current Metabolic Syndrome Events RSSJoslin study identifies protein that produces 'good' fat
A study by researchers at the Joslin Diabetes Center has shown that a protein known for its role in inducing bone growth can also help promote the development of brown fat, a "good" fat that helps in the expenditure of energy and plays a role in fighting obesity.
Drinking in excess associated with increased risk for metabolic syndrome
Those who drink in excess of the U.S. Dietary Guidelines (i.e., men who usually drink more than two drinks per day or women who usually drink more than one drink per day) or those who binge drink are at increased risk for the metabolic syndrome, according to a new study accepted for publication in The Endocrine Society's Journal of Clinical Endocrinology & Metabolism (JCEM).
A single mechanism for hypertension, insulin resistance and immune suppression
Many of the 75 million Americans with essential hypertension also develop diabetes and other complications in addition to their high blood pressure, and researchers have discovered a common molecular mechanism in a strain of rat that explains why such metabolic disorders arise together in mammals.
Gene variants linked to metabolic syndrome and HDL cholesterol levels
Nutrition researchers at Washington University School of Medicine in St. Louis have identified five common genetic variations that increase the risk of metabolic syndrome, a group of factors linked to heart disease and diabetes. Another variant they found appeared to protect against the condition.
Laparoscopic weight-loss surgery improves health of morbidly obese teens
Teenagers' obesity-related medical complications improve just 6 months after laparoscopic gastric banding surgery, a new study found. The preliminary results will be presented at The Endocrine Society's 90th Annual Meeting in San Francisco.
Is it time to revisit the current protein recommendations?
Current protein recommendations were established with the goal of preventing deficiency, but newer research indicates that many adults may benefit from eating more than the minimum requirement.
Current screening test for prediabetes in children misses the diagnosis too often
Obese children, who are at increased risk for prediabetes and type 2 diabetes, may not be getting the most appropriate test to screen for these conditions, a new Canadian study found.
Unexpected finding of molecule's dual role in mice may open new avenue to cholesterol reduction
Researchers have discovered an unknown regulator of fat and cholesterol production in the liver of mice, a significant finding that could lead to new therapies for lowering unhealthy blood levels of cholesterol and fats.
Yerkes researchers find link between psychological stress and overeating
Researchers at the Yerkes National Primate Research Center, Emory University, have found socially subordinate female rhesus macaques over consume calorie-rich foods at a significantly higher level than do dominant females.
Not all fat created equal
It has long been known that type 2 diabetes is linked to obesity, particularly fat inside the belly. Now, researchers at the Joslin Diabetes Center have found that fat from other areas of the body can actually reduce insulin resistance and improve insulin sensitivity.
More Metabolic Syndrome News Articles
 | Freedom from Disease: The Breakthrough Approach to Preventing Cancer, Heart Disease, Alzheimer's, and Depression by Controlling Insulin by Peter Morgan Kash, Jay Lombard Foreword by Mehmet Oz, co-author of YOU: ON A DIET and YOU: AN OWNER'S MANUAL.This ground-breaking book reveals how insulin resistance is linked to heart disease, cancer, Alzheimer’s, overweight, childhood behavioral disorders, depression, high blood pressure, and more. It also provides information on how to get insulin under control.While insulin is most closely associated with diabetes... |
 | The Metabolic Syndrome Program: How to Lose Weight, Beat Heart Disease, Stop Insulin Resistance and More by Karlene Karst The Metabolic Syndrome Program How to Lose Weight, Beat Heart Disease, Stop Insulin Resistance and More Big Belly? High Body Mass Index? High Blood Pressure? If this sounds like you, you may be one of the millions of North Americans with Metabolic Syndrome. Predicted by medical experts as the likely number one risk factor for heart disease-Metabolic Syndrome, or MSX,... |
 | The New Glucose Revolution Low GI Guide to the Metabolic Syndrome and Your Heart: The Only Authoritative Guide to Using the Glycemic Index for Better Heart Health (Glucose Revolution) by Dr. Jennie Brand-Miller, Anthony Leeds, Kaye Foster-Powell Written by the leading authorities on the Glycemic Index, The New Glucose Revolution Guide to the Metabolic Syndrome and Your Heart provides readers with the most up-to-date information about using the GI to reduce their risk of having a heart attack. It explains the importance of slowly digested, low-GI carbohydrates, and offers important dietary guidelines for managing blood glucose levels,... |
 | Overcoming Metabolic Syndrome by Scott Isaacs, Fred Vagnini Twenty-seven Percent of Americans Have Metabolic Syndrome It’s now estimated that 55 million Americans have metabolic syndrome; however, if you’re like most Americans, you may not have ever heard of the syndrome much less understand how it increases your risk of heart disease and stroke. Metabolic syndrome actually is a cluster of disorders, all of which are affected by both genetics... |
 | Toxic Fat: When Good Fat Turns Bad by Barry Sears Toxic Fat: When Good Fat Turns Bad, provides a revolutionary new understanding of our current obesity epidemic by showing that it can be viewed as a form of cancer to be treated using the clinically proven pathway to change the expression of your genes using food as a drug to rid your body of toxic fat. For many of us, one of the first signs of toxic fat is the accumulation of excess body fat.... |
 | The Metabolic Syndrome:: Epidemiology, Clinical Treatment, and Underlying Mechanisms (Contemporary Endocrinology) With an extraordinary need for early intervention and prevention to slow or halt its progression, Metabolic Syndrome is one of the most challenging health problems. Only through an understanding of the science underlying this syndrome can successful interventions be developed and implemented. In The Metabolic Syndrome: Epidemiology, Clinical Treatment, and Underlying Mechanisms, the writers... |
 | The New Glucose Revolution Pocket Guide to the Metabolic Syndrome by Jennie Brand-Miller, Kaye Foster-Powell, Anthony Leeds, Dr. Jennie Brand-Miller The latest medical research clearly confirms that the glycemic index (GI)—an easy-to-understand ranking of foods based on their effect on blood glucose levels—is vitally important for heart health and the prevention of the Metabolic Syndrome (aka Syndrome X and insulin resistance). Slowly digested, low-GI carbohydrates like pasta, grainy breads, and cereals based on wheat bran and... |
| Anesthesia for Genetic, Metabolic, and Dysmorphic Syndromes of Childhood (Baum, Anesthesia for Genetic, Metabolic, adn Dysmorphic Syndromes of Childhood) by Victor C Baum, Jennifer E O'Flaherty Thoroughly updated for its Second Edition, this reference is the only single-source guide to the anesthetic management of children and adults with genetic, metabolic, and dysmorphic syndromes. In a format designed for quick, easy look-up, this edition provides an encyclopedic review of well over 500 distinct syndromes, with up-to-date information, complete current bibliographies, and over 140... | |
 | It Must Be My Metabolism by Reza Yavari A comprehensive plan to help you combat metabolic syndrome, lose weight, and restore overall health First recognized by the World Health Organization in 1998, metabolic syndrome has become one of the hottest topics in health care. A collection of seemingly unrelated medical disorders, metabolic syndrome includes heart disease, excess abdominal fat, sleep problems, infertility, insulin resistance... |
 | The Hershberg Diet: Discover How the Fourth Macro Can Help You Shed Pounds and Beat the Metabolic Syndrome by Melissa Hershberg The Hershberg Diet is not another fad diet, it’s a weight loss system based on hard science. Dr. Melissa Hershberg reveals that the key to lasting weight loss is the “fourth macronutrient.” Because most people — including physicians, nutritionists, and dieticians — recognize only three — protein, carbohydrates, and fat — the discovery of a fourth... |
| © 2008 BrightSurf.com |