Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New genetic link between cardiac arrhythmias and thyroid dysfunction identified

22.09.2009
2 genes represent potential drug targets for both heart and endocrine disease

Genes previously known to be essential to the coordinated, rhythmic electrical activity of cardiac muscle -- a healthy heartbeat -- have now also been found to play a key role in thyroid hormone (TH) biosynthesis, according to Weill Cornell Medical College researchers.

The authors' findings, published online this week by the peer-reviewed journal Nature Medicine, suggest that mutations of either of two gene products -- proteins called KCNE2 and KCNQ1 -- already known to be involved in human cardiac arrhythmias, could also cause thyroid dysfunction.

"It has long been known that the thyroid influences cardiac function and cardiac arrhythmias," says study senior author Dr. Geoffrey W. Abbott, associate professor of pharmacology in medicine at Weill Cornell Medical College, "but our findings demonstrate a novel genetic link between inherited cardiac arrhythmia and thyroid dysfunction."

Additionally, it is the authors' suggestion that assessment of the thyroid status of patients with KCNE2- and KCNQ1-linked cardiac arrhythmias could in some cases reveal a potential endocrine component to their cardiac arrhythmias that may not have been previously determined. This, in turn, could indicate treatment of the thyroid condition, with potentially beneficial effects on cardiac function.

KCNQ1 and KCNE2 were each recognized more than a decade ago as forming potassium channels in cardiac muscle that help end each heartbeat in a timely fashion. Inherited mutations in KCNQ1 and KCNE2 cause ventricular and atrial cardiac arrhythmias, previously presumed to be due entirely to the role of these proteins in cardiac muscle. The researchers have now discovered that KCNQ1 and KCNE2 also form a potassium channel in the thyroid gland.

"When the thyroid does not produce enough TH, a person may experience symptoms such as fatigue and a lowered heart rate, but there is also a more complex interplay between thyroid function, cardiac structure and cardiac arrhythmias. Our new findings may begin to explain some of these interrelationships," explains Dr. Abbott.

While studying mice that had the KCNE2 gene removed from their genome, the researchers observed that the animals developed symptoms of hypothyroidism, especially during pregnancy, and gave birth to pups with dwarfism, alopecia (baldness) and cardiomegaly (enlarged heart).

After allowing the mouse pups to drink milk only from mothers without the genetic alteration, the pups' symptoms were alleviated. The healthy mothers' milk contains normal levels of TH -- essentially acting as a TH replacement therapy. The symptoms were also treated by direct TH supplementation of pups or mothers.

"We then wanted to test what the mechanism was in the mice that caused deletion of the KCNE2 gene to have negative consequences for the thyroid," says Dr. Abbott.

Using micro positron emission tomography (microPET), Dr. Abbott and his team visualized the accumulation in the mouse thyroid of an iodine radioisotope in real-time. They found that absorption of the radioisotope in the thyroid was greatly impaired in mice lacking the KCNE2 gene. They believe that, normally, the KCNQ1-KCNE2 potassium channel helps another protein (the sodium/iodide symporter) to transport iodide into the thyroid.

Without the KCNQ1-KCNE2 potassium channel, the efficiency of iodide absorption by the thyroid is greatly reduced. Because iodide is an essential component of TH, this means that KCNE2 deletion also impairs TH production.

Future studies will now center on determining how applicable the research team's findings in the mouse are to the human population.

"While we have identified KCNQ1 and KCNE2 in both mouse and human thyroid, much additional work is required before we can fully understand how inherited mutations in the genes coding these proteins affect human thyroid function, how this in turn influences the health of human heart and other tissues, and how useful our discoveries will be in developing therapies to treat thyroid and thyroid-related human disease," explains Dr. Abbott.

Cardiac arrhythmias affect up to three million people in the United States. The majority of these suffer from atrial fibrillation, a chronic arrhythmia most often observed in the aging population. Ventricular arrhythmias account for the large majority of the 300,000 cases of sudden cardiac death annually in the United States. Thyroid dysfunction is estimated to affect one to four percent of the world's population.

Additional co-authors include Torsten K. Roepke, Elizabeth C. King and Kerry Purtell from Weill Cornell; Daniel J. Lerner from CV Ingenuity, San Francisco, CA; and Andrea Reyna-Neyra, Monika Paroder,Wade Koba, Eugene Fine and Nancy Carrasco from the Albert Einstein College of Medicine, The Bronx, NY.

The study received support from the National Institutes of Health and the American Heart Association.

Weill Cornell Medical College

Weill Cornell Medical College, Cornell University's medical school located in New York City, is committed to excellence in research, teaching, patient care and the advancement of the art and science of medicine, locally, nationally and globally. Weill Cornell, which is a principal academic affiliate of NewYork-Presbyterian Hospital, offers an innovative curriculum that integrates the teaching of basic and clinical sciences, problem-based learning, office-based preceptorships, and primary care and doctoring courses. Physicians and scientists of Weill Cornell Medical College are engaged in cutting-edge research in areas such as stem cells, genetics and gene therapy, geriatrics, neuroscience, structural biology, cardiovascular medicine, transplantation medicine, infectious disease, obesity, cancer, psychiatry and public health -- and continue to delve ever deeper into the molecular basis of disease and social determinants of health in an effort to unlock the mysteries of the human body in health and sickness. In its commitment to global health and education, the Medical College has a strong presence in places such as Qatar, Tanzania, Haiti, Brazil, Austria and Turkey. Through the historic Weill Cornell Medical College in Qatar, the Medical College is the first in the U.S. to offer its M.D. degree overseas. Weill Cornell is the birthplace of many medical advances -- including the development of the Pap test for cervical cancer, the synthesis of penicillin, the first successful embryo-biopsy pregnancy and birth in the U.S., the first clinical trial of gene therapy for Parkinson's disease, the first indication of bone marrow's critical role in tumor growth, and most recently, the world's first successful use of deep brain stimulation to treat a minimally conscious brain-injured patient. For more information, visit www.med.cornell.edu.

John Rodgers | EurekAlert!
Further information:
http://www.cornell.edu

More articles from Life Sciences:

nachricht What happens in the cell nucleus after fertilization
06.12.2016 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Researchers uncover protein-based “cancer signature”
05.12.2016 | Universität Basel

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

Simple processing technique could cut cost of organic PV and wearable electronics

06.12.2016 | Materials Sciences

3-D printed kidney phantoms aid nuclear medicine dosing calibration

06.12.2016 | Medical Engineering

Robot on demand: Mobile machining of aircraft components with high precision

06.12.2016 | Power and Electrical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>