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 Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery
20.01.2017 | GSI Helmholtzzentrum für Schwerionenforschung GmbH

nachricht Seeking structure with metagenome sequences
20.01.2017 | DOE/Joint Genome Institute

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

An innovative high-performance material: biofibers made from green lacewing silk

20.01.2017 | Materials Sciences

Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery

20.01.2017 | Life Sciences

Bodyguards in the gut have a chemical weapon

20.01.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>