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.