Produced by the Office of Communications // September 22, 2011
Study reveals common gene variant associated with aortic dissection
Richard Holbrooke, John Ritter, Lucille Ball, 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 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 were published in the Sept. 11, 2011, advance online issue of Nature Genetics. Senior author is Dr. Dianna Milewicz, professor of internal medicine and holder of the the President George H.W. Bush Chair in Cardiovascular Research.
“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 and heads the 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 Dr. Scott LeMaire, professor of surgery and director of research in the Division of Cardiothoracic Surgery at Baylor 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.”
Dr. Merry-Lynn McDonald, of Baylor, and Dr. Dong-chuan Guo, assistant professor of internal medicine, contributed equally along with LeMaire as co-first authors on the article.
Other UTHealth co-authors include Dr. Charles Miller, III, professor of cardiothoracic and vascular surgery; Dr. Ralph Johnson, assistant professor of internal medicine; Dr. Hazim Safi, professor and chair of the Department of Cardiothoracic and Vascular Surgery; and Dr. Anthony Estrera, professor of cardiothoracic and vascular surgery.
Baylor co-investigators include Dr. Suzanne Leal, professor of molecular and human genetics; Dr. John Belmont, professor of molecular and human genetics; Ludivine Russell, cardiothoracic surgery research coordinator; Dr. Mir Reza Bekheirnia, clinical fellow in the Department of Molecular and Human Genetics; Dr. Luis Franco, assistant professor of molecular and human genetics; Mary Nguyen, cardiothoracic surgery laboratory technician; Dr. Molly Bray, associate professor of pediatrics; and Dr. Joseph Coselli, professor and chief of the Division of Cardiothoracic Surgery. Harvard Medical School co-investigators are Dr. Simon Body, associate professor of anesthesia; Dr. Christine Seidman, professor of genetics and medicine; Dr. Jonathan Seidman, professor of genetics; and Dr. Eric Isselbacher, associate professor medicine.
Other co-investigators are Dr. Reed Pyeritz, Perelman School of Medicine at the University of Pennsylvania; Dr. Joseph Bavaria, Perelman School of Medicine at the University of Pennsylvania; Dr. Richard Devereux, Weill Cornell Medical College; Dr. Cheryl Maslen, Oregon Health and Science University; Dr. Kathryn Holmes, Johns Hopkins University School of Medicine; and Dr. Kim Eagle, University of Michigan Medical School.
— Deborah Mann Lake, Office of Advancement, Media Relations
Juarez receives ASM, NIH fellowships
A doctoral student in microbiology and molecular genetics has received two research fellowships to study the spread of E. coli, a hard-to-treat bacterium that can lead to food poisoning.
Jennifer Juarez received fellowships from the American Society for Microbiology (ASM) and the National Institutes of Health (NIH). The ASM fellowship supports professional development, and the NIH fellowship provides a two-year stipend of up to $56,232.
Juarez is a doctoral student in microbiology and molecular genetics at the Graduate School of Biomedical Sciences, which trains research scientists and scientist-educators. The school is overseen by UTHealth and The University of Texas MD Anderson Cancer Center.
While most strains of E. coli are harmless, some have been linked to diarrhea, vomiting, and nausea. Undercooked meat is not the only source of harmful E. coli. It is sometimes found in contaminated water, and it can be spread by people with poor hygiene. Disease associated with E. coli can be fatal.
Juarez’s research on how the bacterium reproduces is being conducted in the laboratory of Dr. William Margolin, a professor of microbiology and molecular genetics. He also is on the faculty of the GSBS.
“Jennifer is studying how bacterial cells divide, a process required for bacterial propagation in any environmental niche including in the human body during infection,” Margolin said. “Despite much research on bacteria, the molecular mechanisms for cell fission are not well understood.
“Understanding the mechanisms bacteria use to divide and proliferate will pave the way for the development of novel antibacterial treatments. This is especially critical now as bacteria are become increasingly resistant to currently available antibiotics,” he added.
Juarez received the ASM’s Robert D. Watkins Graduate Research Fellowship, which seeks to increase the number of graduate students from underrepresented groups completing doctoral degrees in the microbiological sciences. This year, 44 applications were received, and seven were awarded.
She also received the NIH’s Ruth L. Kirschstein National Research Service Award for Individual Predoctoral Fellowship to Promote Diversity in Health Related Research, which will be funded by the National Institute of General Medical Sciences.
— Robert Cahill, Office of Advancement, Media Relations
Faculty development leave proposals due Nov. 1
Proposals for Faculty Development Leave are due Nov. 1 in the Office of Faculty Affairs, MSB G.420.
Proposals may be submitted twice a year: Nov. 1 and April 1.
For questions, call Faye Viola, 713.500.5101.
NRC abstracts due Oct. 14
The Neuroscience Research Center is requesting abstracts for its 18th Annual Poster Session, which will be held 10 a.m.–noon, Saturday, Dec. 3 in the Medical School’s Leather Lounge.
Abstracts are due Oct. 14. Awards will be given for the top three Graduate School of Biomedical Sciences submissions as well as for the top three postdoctoral/research fellows.
The Poster Session is open to all UTHealth faculty members, research scientists, residents, graduate students, postdoctoral fellows, and medical students. A limited number of positions are available.
Events to know
Bioterrorism and Emerging Infectious Disease Preparedness and Response Series: Dr. Wendy Keitel (Baylor College of Medicine) presents, “Influenza Strains, Supply & Schedules: Giving the Right Dose at the Right Time.”
Noon, MSB B.603.
GSBS Town Hall Meeting with Presidents Giuseppe Colasurdo and Ronald DePinho.
Noon–1 p.m., Onstead Auditorium, BSRB, 6767 Bertner, Third Floor.
Bring lunch; drinks will be provided. Contact Brenda Gaughan, 713.599.9857.
Biochemistry Seminar Series: Dr. Matthew Baker (Baylor College of Medicine) presents, “Modeling Macromolecular Machines at Near-Atomic Resolutions.”
Noon, MSB 2.135.
The International Association of Administrative Professionals, Medical Center Chapter, presents, “How to Write the Perfect Resume and Cover Letter.”
Holiday Inn, 6800 Main at Holcombe Boulevard.
Dinner is offered. For details and registration, contact Melissa Menchaca, 713.792.6670.
Research Coordinator Forum: Lance Nickens, president, The Patient Recruiting Agency, presents, “Recruitment Practices for Clinical Trials.”
11:30 a.m.–1 p.m., MSB 2.135.
Lunch will be available for the first 50 attendees.
Department of Psychiatry & Behavioral Sciences Grand Rounds: Dr. Ian Butler, professor of neurology and pediatrics, presents, “One Observation Leads to Two Observations and a Case Report Leads to a Career in Child Neurology and Mentoring.”
Noon–1 p.m., HCPC Auditorium.
Contact Kristi Rowell for details.
Topics in Neurobiology of Disease: Stem Cells and Regenerative Medicine: Dr. Charles Cox, professor of pediatric surgery, presents, “Cellular Therapy for Traumatic Brain Injury.”
Noon, MSB 7.037.
Sponsored by the Neuroscience Research Center and GSBS.
Microbiology and Molecular Genetics Seminar Series: Dr. Slavena Vylkova (postdoctoral fellow, laboratory of Dr. Michael Lorenz) presents, “Environmental pH modulation by Candida albicans.”
10:45 a.m., MSB 2.135.
Multiple Sclerosis Patient Education Day.
8 a.m.–1:15 p.m., Marriott Houston Westchase.
RSVP for this free event by Sept. 23 to 713.500.7050 or to Sherri Mccollum.
Bioterrorism and Emerging Infectious Disease Preparedness and Response Series: Dr. Theresa Koehler, DuPont Professor and interim chair of the Department of Microbiology & Molecular Genetics, presents, “Our Culture of Responsibility.”
Noon, MSB B.610.
Department of Integrative Biology and Pharmacology Seminar Series: Dr. Masao Kakoki (University of North Carolina at Chapel Hill) presents, “Cardiovascular pathogenesis in mice underexpressing transforming growth factor beta1.”
4 p.m., MSB 2.135.
Free flu vaccine for UTHealth students.
11 a.m.–1 p.m., MSB B.645.
Starting Oct. 10, free flu vaccines for UTHealth students are available at UTHealth Student Health Services, UTPB 1010, between 9–11 a.m. and 2–4 p.m. No appointment is necessary.
Department of Psychiatry & Behavioral Sciences Grand Rounds: Dr. Vineeth John, associate professor of psychiatry, presents, “The Leader’s Brain: The Neuroscience of Leadership.”
Noon–1 p.m., HCPC Auditorium.
Contact Kristi Rowell for details.
Family & Community Medicine Grand Rounds: Dr. Judianne Kellaway, Associate Professor of Ophthalmology, presents, “Diabetic & Hypertension Retinopathy.”
1–2 p.m., MSB 2.135.
6th Annual Postdoktoberfest.
5–7 p.m., McGovern Commons.
All postdoctoral fellows invited. Bavarian style food and drink will be served. For details, contact Leslie Beckman.
UTHealth Postdoc Dr. Rodrigo Fernandez-Valdivia, Institute of Molecular Medicine, received the 2011 Postdoctoral Professional Development and Enrichment Award from the FASEB MARC Program. Funded by a grant from the NIH, the award was established to recognize outstanding achievement by an early career life scientist from an underrepresented group. These awards are primarily intended for advanced postdoctoral fellows or new assistant professors who will be able to utilize these resources to gain knowledge, skills, and training to enrich their competitiveness for research funding, publication in top tier journals, and employment in prestigious research intensive settings.
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