Two links in the genetic chain could predispose some people to a fatal lung disease.
Scientists at Johns Hopkins identified the genetic culprits that trigger a hereditary form of a fatal lung disease ? idiopathic pulmonary fibrosis.
“It’s kind of been a mysterious disease,” said Dr. Mary Armanios, assistant professor of oncology at the Johns Hopkins Kimmel Cancer Center and lead author of the report. “It just shows up and eventually kills people.”
Their findings, published in the March 29, 2007, issue of the New England Journal of Medicine, may guide diagnosis and treatment for families that inherit genes for the disease, as well as for those that develop non-inherited forms.
The disease takes its names from fibrosis, or scarring of the lung tissue, which restricts lung function over time. Most people live three to five years after contracting the disease and there are no known approved treatments.
About 200,000 Americans have it, according to the National Institutes of Health. About 50,000 newcases are diagnosed each year, affecting mostly people 50 to 75 years of age.
As many as 20 percent of IPF sufferers are thought to have inherited genetic mistakes that predispose them to the disease, and until now, these flaws remained unknown.
Hopkins researchers found mutations in two genes that regulate the enzyme telomerase, which keeps the ends of chromosomes, or telomeres, from fraying. In natural use, bits of the telomere break off until there is nothing there to protect the valuable genetic material from damage and the cell dies.
While cancerous cells produce too much of the enzyme, and so avoid natural cell death, people with inherited forms of pulmonary fibrosis may not have enough to keep healthy cells ticking, Armanios said.
In the current study, mutation carriers had telomeres about one-third the length of those in relatives with no genetic flaws.
Gene tests are currently not available, but scientists are developing tests to assess a person?s risk of the disease by screening telomere length.
“If we follow the genetic threads of families that inherit IPF, it may lead us to understand the genetic properties causing more common forms of the disease,” Armanios says.
Patients with non-inherited IPF also may have short telomeres, Armanios said.
“There may be other causes for short telomeres, such as older age and smoking, which also happen to be the main risk factors for IPF.”
