Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Gene variant heightens risk of severe liver disease in cystic fibrosis

10.09.2009
Researchers at the University of North Carolina at Chapel Hill have discovered a genetic risk factor for severe liver disease in people with cystic fibrosis.

Those who carry a particular variant of the SERPINA1 gene (also known as alpha-1-antitrypsin or alpha-1-antiprotease) are five times more likely to develop cirrhosis and other liver complications than patients who carry the normal version of the gene.

The study, which appears in the Sept. 9 issue of the Journal of the American Medical Association (JAMA), could lead to earlier detection and diagnosis of cystic fibrosis liver disease and better treatment options for the patients affected by the disease. In addition, it could pave the way for similar studies in more common forms of liver disease.

"I predict that as we uncover more risk factors of liver disease in cystic fibrosis we may also find that they play a role in how rapidly people with a more common malady, such as viral hepatitis, develop liver complications (or "fibrosis")," said senior study author Michael R. Knowles, M.D., professor of pulmonary and critical care medicine at UNC.

Cystic fibrosis is the most common fatal genetic illness among Caucasians. In the disease, defects in the CFTR gene cause the lungs, intestines and pancreas to become clogged with mucus, resulting in breathing problems and other difficulties. Though every patient with cystic fibrosis carries mutations in both copies of their CFTR gene (one inherited from the mother and one from the father), symptoms can vary widely from patient to patient. For instance, about five percent of cystic fibrosis patients develop liver disease so severe it requires a liver transplant.

For the last decade, researchers have been investigating what other genetic factors might modify the effects of the disease-causing mutations in the CFTR gene, further altering the biological conditions under which the disease unfolds to either make it milder or more severe. Several genes have emerged as potential "genetic modifiers," and studies to replicate some of those findings have recently been accomplished.

In this study, the UNC researchers collaborated with an international team of scientists to compile the largest number of samples ever from cystic fibrosis patients with severe liver disease. The study was initially conducted in 124 cystic fibrosis patients with severe liver disease and 843 cystic fibrosis patients without liver disease. The team evaluated nine sequence variants in five genes that previous studies had suggested might be associated with liver disease.

They found that more cystic fibrosis patients with liver disease had a particular version of the SERPINA1 gene -- called the Z allele – than patients without liver disease, indicating that the gene variant plays a role in the development of this ailment. The researchers confirmed their results in a separate set of cystic fibrosis patients, 136 with liver disease and 1088 without.

According to lead study author Jaclyn R. Bartlett, Ph.D., discovering such risk factors will enable clinicians to identify cystic fibrosis patients who may be predisposed to develop liver disease. "We also hope that further research will show how the presence of this particular gene affects the liver on a molecular level in cystic fibrosis patients," said Bartlett, a research associate scientist at UNC.

Aided by their international collaborators, the researchers are now searching for genetic modifiers associated with other complications of cystic fibrosis, including lung disease, intestinal obstruction and diabetes.

Funding for the studies led at UNC came from the Cystic Fibrosis Foundation and the National Institutes of Health. Study co-authors from UNC include Kenneth J. Friedman, Ph.D., former research assistant professor of pathology; Rhonda G. Pace, research specialist; William B. Hannah, medical student; Yunfei Wang, graduate student; Fei Zou, Ph.D., associate professor of biostatistics; Lawrence M. Silverman, Ph.D., former professor of pathology and laboratory medicine; Fred A. Wright, Ph.D., professor of biostatistics; and Ethan M. Lange, Ph.D., assistant professor of genetics.

Les Lang | EurekAlert!
Further information:
http://www.unc.edu

More articles from Life Sciences:

nachricht Cryo-electron microscopy achieves unprecedented resolution using new computational methods
24.03.2017 | DOE/Lawrence Berkeley National Laboratory

nachricht How cheetahs stay fit and healthy
24.03.2017 | Forschungsverbund Berlin e.V.

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

Im Focus: Researchers Imitate Molecular Crowding in Cells

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Argon is not the 'dope' for metallic hydrogen

24.03.2017 | Materials Sciences

Astronomers find unexpected, dust-obscured star formation in distant galaxy

24.03.2017 | Physics and Astronomy

Gravitational wave kicks monster black hole out of galactic core

24.03.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>