For years now, diet pills have been linked to a condition known as primary pulmonary hypertension, a lung disease that is usually fatal if untreated.
Now Vanderbilt University researchers can point to the exact genetic mutation behind PPH, a disease that affects roughly 300 people each year, according to a study published Thursday in Nature Genetics.
A team led by Dr. James E. Loyd isolated the bone morphogenic protein receptor two gene, or BMPR2.
"When mutated, the gene causes cells to grow and clog the inside of blood vessels in the lungs, similar to clogged arteries in the heart," said Loyd, a professor of medicine at Vanderbilt University Medical Center.
"This really begins a true scientific understanding of what causes PPH," he said. "It's in the transforming growth factor beta (TGFb)family, which is a large family of different proteins that regulate cell growth and proliferation."
Mutations that trigger the disease are spread across 13 different coding regions of the gene.
"TGFb is a growth suppressor gene, so this gene, BMPR2, normally prevents the cells from growing," Loyd said. "When it mutates or is defective, the suppressor is stopped and it allows the cells to grow unregulated and they ultimately block the blood vessels."
Doctors can treat PPH, but the medicine has side effects and costs $50,000 per dose. It also needs to run continuously through an intravenous tube.
While a viable or less-expensive treatment alternative is still only an idea, locating the gene is the first step toward that goal, said Dr. Norman H. Edelman, consultant with the American Lung Association.
"If you've got the gene and you know what protein it expresses, then you have a real strong clue toward unraveling the mechanisms that cause the disease," he said.
Generally, PPH is akin to heart disease, with lung passages becoming too blocked for blood to flow normally to the rest of the body. Patients may pass out or become short of breath.
PPH can be genetically inherited or result from the use of diet pills.
The diet suppressant aminorex was behind a European outbreak of PPH in the early 1970s before officials pulled it from the marketplace. The use of fenluramine/dexfenfluramine was documented as a cause in 1997, after a multitude of symptoms struck dieters, most of them women.
As a result, the FDA issued warnings about diet pills.
"Identifying the disease will allow us to start to answer the question of why do women get this disease more than men," Loyd said.
He said more research is called for in order to fine-tune these conclusions.
"Hopefully we will eventually be able to get to the point where we understand how the gene works and what it does, and not only whether you are at risk or not, but also at what age you might be at risk," Loyd said.
