Richard Holbrooke, John Ritter, Lucille Ball, Jonathan Larson and Great Britain's King George II were all taken by the same silent killer: an acute aortic dissection.
Now, scientists led by researchers at The University of Texas Health Science Center at Houston (UTHealth) and Baylor College of Medicine (BCM) have found an association with a common genetic variant in the population that predisposes people to acute dissections and can approximately double a person's chances of having the disease.
An aortic aneurysm is an enlargement or ballooning of the aorta in the segment where it comes out of the heart (thoracic aortic aneurysm). The natural history of a thoracic aortic aneurysm is to enlarge without symptoms over time, leading to instability of the aorta and ultimately an acute aortic dissection. The dissection is a tear in the aorta that allows blood to flow within its layers. It is a life-threatening event, with up to 40 percent of patients dying suddenly.
Although the average age of a person who suffers an aortic dissection is early 60s, the disease can strike at any age. Since the majority of individuals have an aortic aneurysm prior to dissection, identification of these aneurysms is critical since the aneurysm can be surgically repaired to prevent the aortic dissection, which typically occurs when the diameter of the aneurysm reaches twice that of the normal aorta. Therefore it is important to know who is at risk for this disorder.
The results of the research are published in the Sept. 11, 2011 advance online issue of Nature Genetics. Senior author is Dianna M. Milewicz, M.D., Ph.D., professor and the President George H.W. Bush Chair in Cardiovascular Research at The University of Texas Medical School at Houston, part of UTHealth.
"This is the first time we've found an association with a common genetic variant in the population that predisposes people to thoracic aortic aneurysms that cause acute aortic dissections. This variant in the DNA is on chromosome 15 (15q21.1) and involves a gene called FBN1. We already know that mutations in this gene cause Marfan syndrome, which is a genetic syndrome that strongly predisposes individuals to aortic dissections but also causes people to grow tall and have weak eyes," said Milewicz, who is also director of the Division of Medical Genetics at the UTHealth Medical School and heads the UTHealth John Ritter Research Program in Aortic and Vascular Diseases. "Although patients with aortic dissection in our study did not have Marfan syndrome, this study suggests that the same pathways are involved in causing aortic dissections in patients with and without Marfan syndrome."
Milewicz said the research has implications for using drugs to treat patients to prevent aortic aneurysms from even forming, such as losartan, which is now being tested in clinical trials for people with Marfan syndrome. "Whether they have Marfan or the common variant in FBN1, it may be the same pathway and we may be able to treat these patients the same way. That means that what we learn in treating patients with Marfan syndrome has implications for this larger group of individuals with thoracic aortic disease," she said.
"Over the past two decades, there has been remarkable progress in understanding the causes of aortic aneurysms and dissections in patients with inherited disorders, particularly Marfan syndrome. However, up to 80 percent of patients with thoracic aortic aneurysms and dissections do not have a known inherited cause, and the genetic factors that impact susceptibility to aortic disease in these patients are poorly understood," said the study's first author Scott A. LeMaire, M.D., professor of surgery and director of research in the Division of Cardiothoracic Surgery at BCM and surgeon at the Texas Heart Institute at St. Luke's Episcopal Hospital. "This gap in our understanding of 'sporadic' disease motivated us to conduct this study, which would not have been possible without the tremendous efforts of a large team of dedicated collaborators."
The study examined more than 1,300 patients who had sporadic thoracic aortic disease, meaning they did not have a known family genetic history or genetic syndrome associated with the disease. The patients came from the Memorial Hermann Heart & Vascular Institute, the Texas Heart Institute and Harvard Medical School, as well as from the National Institutes of Health GenTAC program, which includes the Perelman School of Medicine at the University of Pennsylvania, Johns Hopkins University School of Medicine, Weill Cornell Medical College of Cornell University and Oregon Health and Science University.
The discovery was made possible by a grant from the NIH that funded the Specialized Center for Clinically Oriented Research in Aortic Diseases, a multi-institutional collaboration in the Texas Medical Center. The title of the article is "Genome-wide association study identifies a susceptibility locus for thoracic aortic aneurysms and aortic dissections spanning FBN1 at 15q21.1." Merry-Lynn N. McDonald, Ph.D., at BCM; and Dong-chuan Guo, Ph.D., assistant professor of internal medicine at UTHealth, contributed equally along with LeMaire as co-first authors on the article.
Other UTHealth co-authors include Charles C. Miller, III, Ph.D., professor of cardiothoracic and vascular surgery; Ralph J. Johnson, Ph.D., assistant professor of internal medicine; Hazim Safi, M.D., professor and chair of the Department of Cardiothoracic and Vascular Surgery; and Anthony L. Estrera, M.D., professor of cardiothoracic and vascular surgery.
BCM co-investigators include Suzanne M. Leal, Ph.D., professor of molecular and human genetics; John W. Belmont, M.D., Ph.D., professor of molecular and human genetics; Ludivine Russell, M.S., cardiothoracic surgery research coordinator; Mir Reza Bekheirnia, M.D., clinical fellow in the Department of Molecular and Human Genetics; Luis M. Franco, M.D., assistant professor of molecular and human genetics; Mary Nguyen, B.S., cardiothoracic surgery laboratory technician; Molly Bray, Ph.D., associate professor of pediatrics; and Joseph S. Coselli, M.D., professor and chief of the Division of Cardiothoracic Surgery. Harvard Medical School co-investigators are Simon C. Body, M.B., Ch.B., M.P.H., associate professor of anesthesia; Christine Seidman, M.D., professor of genetics and medicine; Jonathan G. Seidman, Ph.D., professor of genetics; and Eric M. Isselbacher, M.D., associate professor medicine.
Other co-investigators are Reed E. Pyeritz, M.D., Ph.D., Perelman School of Medicine at the University of Pennsylvania; Joseph E. Bavaria, M.D., Perelman School of Medicine at the University of Pennsylvania; Richard Devereux, M.D., Weill Cornell Medical College; Cheryl Maslen, Ph.D., Oregon Health and Science University; Kathryn W. Holmes, Johns Hopkins University School of Medicine, M.D., M.P.H; and Kim Eagle, M.D., University of Michigan Medical School.
Media note: For requests to interview Dr. Milewicz, please contact Deborah Mann Lake, senior media relations specialist, UTHealth, 713-500-3304. For requests to interview Dr. LeMaire, please contact Gracie Gutierrez, senior communication specialist, Baylor College of Medicine, 713-798-4710.
Deborah Lake | EurekAlert!
Further reports about: > BCM > Cardiothoracic > Division > FBN1 > Genetics > Medical Wellness > Medicine > Prostate Surgery > UTHealth > Universität Harvard > aortic > aortic aneurysms > cardiothoracic surgery > genetic variant > health services > thoracic aortic aneurysms > thoracic surgery > vascular cells > vascular surgery
NYSCF researchers develop novel bioengineering technique for personalized bone grafts
18.07.2018 | New York Stem Cell Foundation
Pollen taxi for bacteria
18.07.2018 | Technische Universität München
For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.
To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...
For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.
Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...
Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.
A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...
Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.
"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....
Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.
Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...
13.07.2018 | Event News
12.07.2018 | Event News
03.07.2018 | Event News
18.07.2018 | Life Sciences
18.07.2018 | Materials Sciences
18.07.2018 | Health and Medicine